Barter syndrome:

Bartters syndrome consists of metabolic hypokalaemia, alkalosis, hypercalciuria,

normal blood pressure and elevated plasma renin and aldosterone. It is an
autosomal-recessive condition leading to tubular defects in sodium chloride
transport and increased intrarenal production of PGE2. A renal biopsy is
diagnostic.
Type 1: Na+K+-2 cotransporter;
Type 11: K+ channel;
Type 111: l- channel defects.
Treatment: Cox-1 or Cox-2 inhibitors.




Rickets:

Disorder Serum
calcium
Serum
phosphate
Alkaline
phosphatase
Parathyroid
hormone
Hypophosphataemic
rickets
Normal or
decreased
Decreased Increased Normal
Vitamin D-dependent
rickets
Decreased Normal or
decreased
Increased Increased
Hyperparathyroidism Increased

Decreased Increased Increased
Nutritional rickets Decreased Decreased

Increased Increased

Hypophosphatasia is an AR recessive disorder characterised by decreased alkaline
phosphate activity.

Zinc
This describes acrodermatitis enteropathica (Zinc deficiency). Presentation
includes a history of :
chronic diarrhoea, perianal and perioral rashes or lesions, reddish hair and alopecia
ocular changes e.g. blepharitis, conjunctivitis, photophobia and corneal dystrophy

Vitamin B1:
Thiamine (vitamin B1) deficiency, results in Beri-beri. Clinical features include
lethargy, restlessness, vomiting, tachypnoea, cyanosis and a characteristic aphonic
cry. Peripheral neuritis, paraesthesia of the toes and feet, calf tenderness and
decreased reflexes may occur at a later stage. Vitamin B1 is neutralised by boiling.

Breast feeding:
Short-term benefits of breastfeeding include decreased incidence of:
GIT infection
Atopic disease
Ear infections
NEC in preterms and low birth weight babies
Systemic infections in preterms

Studies carried out have provided evidence indicating that breastfeeding decreases
risk factors for the development of cardiovascular disease at an older age by
decreasing:
1. Blood pressure: blood pressure in adults studied was lower in individuals
who were breast fed when compared to those who were formula fed.
Prevalence of hypertension was decreased by 17%, ischaemic heart disease
by 16% and stroke / TIAs by 15 %
2. Decreased LDL:HDL cholesterol ratio : breast feeding is associated with an
increased in total and LDL cholesterol concentrations in infancy, but
decreased values in adult life.
3. Decreased incidence of obesity
Breast feeding was not found to be protective against the development of
inflammatory bowel disease, whilst evidence to support association between
breastfeeding and the development of neoplastic disease is inconclusive.

Allergy:
Type I hypersensitivity there are high levels of circulating IgE. This sort of
reaction produces food allergy with serious signs and symptoms of anaphylaxis.
Type II hypersensitivity is caused by antibody dependent cytotoxicity.
Immune complexes mediate type III hypersensitivity and there is evidence of
higher levels of circulating complexes containing IgE and IgG in food allergic
patient

Duane syndrome
Duane syndrome is a sporadic condition that occurs due to congenital hypoplasia
of the abducent (VI) cranial nerve, thus impairing abduction on lateral gaze. The
occulomotor takes over innervation of the lateral rectus with resultant globe
retraction on adduction of the eye. Usuially unilateral and an isolted finding, but it
can be associated with Marcus Gunn jaw winking syndrome and Goldenhars.
Surgery is required to fix the malalignment.
Browns syndrome
Browns syndrome results due to an abnormality of the superior oblique tendon
leading to an inability to look up on adduction of the eye affected. It can either be
congenital or secondary to trauma or infection e.g. sinusitis. Treatment involves
use of steroids, together with antibiotics. Surgical intervention is required if
syndrome is congenital.
Marcus Gunn syndrome
Marcus Gunn jaw winking syndrome is due to abnormal synergy between the
levator and the lateral pterygoid muscle. On opening and deviating the jaw to the
side opposite of the eye affected, the eyelid elevates. Surgical treatment is required.
Neurof ibromatosis 1:
Early cutaneous signs of NF include cafe-au-lait spots and axillary freckling.
Diagnosis of central NF is confirmed on slit lamp examination of the eye, which
reveals Lisch nodules (hyperpigmented iris harmatomas). Peripheral NF (NF1)
tends to be associated with skin neurofibromas and multiple cafe-au-lait spots (6 or
more >5mm in prepubertal children, >15mm in postpubertal children). Central NF
(NF2) is associated with number of neural tumours including eigth-nerve sheath
neurofibromas, meningioma, glioma and plexiform neuroma. Cutaneous
neurofibromas occur with less frequency than in peripheral NF. Associated
abnormalities include scoliosis, orbital haemangioma, local gigantism of a limb,
phaeochromocytoma, renal artery stenosis, pulmonary fibrosis, obstructive
cardiomyopathy and fibrous dysplasia of bone.
Risk of Developing hydrocephalus due to acqueductal stenosis
Developing malignant neoplasms like neurofibrosarcoma, Phaeochromocytoma,
Wilms and Optic glioma.

Von Hippel Lindau:
Autosomal dominant. Involves multiple organs-Hemangioblastoma of cerebellum,
spinal cord, medulla, retina.
Cystic lesion of kidneys, pancreas, liver.
Phaeochromocytoma common.

FEBRILE SEIZURE
Incidence of epilepsy is 9% when there are several risk factors present.

Risk factors include-Atypical febrile seizures
Positive family history of epilepsy
1
st
episode < 9 months of age.
Developmental delay
Pre- existing neurological disorders.

Foot drop:
The common peroneal (L5, S1) nerve arises from the division of the sciatic nerve
in the popliteal fossa. It passes close to the head of the fibula and can be damaged
by pressure in this area. It divides into a superficial and a deep branch. The deep
peroneal nerve supplies the tibialis anterior, extensor hallucis longus and extensor
digitorum longus muscles, which dorsiflex the foot and toes. The superficial nerve
supplies the peroneus longus and brevis muscles, which evert the foot.
Damage to the posterior tibial nerve produces weakness of planter flexion and
inversion of the foot.


Asperger syndrome:
Aspergers syndrome is a condition at mild end of the autistic spectrum. There is
normal early language development & intellectual functioning . In autism, there is
severe language and intellectual impairment. Other features like impairment in
social interaction, stereotypical behaviour and difficulty in communication are
common in both. However Aspergers Syndrome may go undiagnosed in a few
cases.
Group social skills training is the hallmark of the intervention.
As in the case of Autism, it is picked up and diagnosis usually made by 3 years of
age.

Tonsillectomy:
Absolute indications: Enlarged tonsils that cause upper airway obstruction, severe
dysphagia, sleep disorders, or cardiopulmonary complications; peritonsillar abscess
unresponsive to medical management and drainage; tonsillitis resulting in febrile
convulsions; tonsils requiring biopsy to define tissue pathology
Relative indications: Three or more tonsil infections per year despite adequate
medical therapy; persistent foul taste or breath due to chronic tonsillitis; chronic or
recurrent tonsillitis.

Gaseous exchange:
Gas exchange can occur in the final seven branches of the bronchoalveolar tree
(the respiratory zone). The first 16 branches of the bronchial tree are collectively
known as the conducting zone. The equilibration of gases takes about 0.25 s in the
resting lung. Only about 1.5% of oxygen is carried in solution in the plasma.
Carbon dioxide is more water-soluble than oxygen, between 5 and 10% is carried
in dissolved form and this is the predominant method of carriage of CO
2


Eating disorders:
The main differential diagnoses of eating disorders are anorexia and bulimia.
However, for a diagnosis of anorexia the weight must be > 15% below the
expected weight, with amenorrhoea defined as the continuous absence of three
menstrual cycles. Binge episodes and fasting episodes can be seen in both anorexia
and bulimia, but purging behaviours, e.g. laxatives and diuretics are more
characteristic of bulimia. Depression and obsessivecompulsive disorder are
frequently associated with anorexia, which has a high long-term mortality of 18
20%. Predisposing factors for bulimia include a history of anorexia, being
overweight, mood disorder and borderline personality disorder as well as illicit
drug use. The prognosis in bulimia is variable. Both conditions are treated with
psychotherapy, cognitive therapy and self-help groups. Antidepressants can be
useful in bulimia where fluoxetine is used (10 mg/day).
Bulimia nervosa comprises: a preoccupation with food associated with episodes of
gross overeating or 'bingeing'; a fear of fatness; and the development of techniques
to counteract the fattening effect of binges, (self-induced vomiting, use of
laxatives).
Bulimia is far more common in girls. In some cases of bulimia there is evidence of
a previous episode of anorexia but most often bulimia develops de novo as a
syndrome in its own right. The disorder tends to persist. It is often kept secret from
others and the repetitive eating binges can interfere with social relationships, the
patient becoming guilty and depressed. The repeated vomiting and/or purging may
lead to a variety of physical side-effects ranging from eroded dental enamel to
hypokalemia and impaired renal function. Cardiac arrhythmias may be a
consequence of electrolyte abnormalities.
The current treatment of choice is cognitive-behavioural therapy
Mental health assessment;
A referral for a specialist mental health assessment is mandatory when there are
signs suggestive of a major psychotic illness, major emotional illness, (e.g.
obsessional-compulsive disorder or school refusal) or eating disorders if symptoms
have persisted for more than 3 months. Referral is also strongly recommended
when children present with a suicide attempt or there is disclosure of sexual abuse
or for perpetrators of sexually abusive activity. It is also probably recommended
for conduct disorders, poor family function significantly impairing maturation and
development, alcohol, solvents and opiates dependency and poor coping with the
psychological effects of chronic physical illness or handicap.

Diffusing capacity:
Diffusing capacity of the lung, or transfer factor, represents the rate at which a gas
will diffuse from the alveoli into the blood. It is measured using carbon monoxide.

Causes of a decrease in transfer factor: diffuse infiltration, pulmonary fibrosis,
pneumonia, pulmonary hypertension, multiple pulmonary emboli, low cardiac
output, anaemia and emphysema.

Causes of an increase in transfer factor: asthma, bronchitis, alveolar bleeding,
hyperkinetic states, exercise, left-to-right shunts and polycythaemia

Lung development:
Endodermal foregut bud with surrounding mesoderm arises at 4 weeks of age and,
by 16 weeks, full complement of airways is complete. Alveolisation begins at 30
wedks and continues post-term well beyond the age of 2 years. Airway smooth
muscle are found at term down to smallest terminal bronchioles. Fetal breathing is
established by 9 weeks of age. When air breathing establishes, lung fluid secretion
stops and is reabsorbed, surfactant is released and pulmonary vascular resistance
falls to allow perfusion.


Anatomy

The median nerve arises from the lateral and medial cords of the brachial plexus, at
C6-8, T1. It supplies the radial half of the flexor digitorum profundus, along with
the lateral two lumbricals, the thenar eminence and provides sensation to the
palmar aspect of the lateral three and a half fingers. It has no branches within the
arm.
Damage to the ulnar nerve at the elbow leads to inability to adduct the thumb and
spread the fingers. Claw hand results due to the inability to flex the metacarpo-
phalangeal joints, or extend the inter-phalangeal joints of the ring and little fingers.
Loss of sensation of the medial side of the palm and medial one and a half fingers
and wasting of the hypothenar eminence also occurs.
C7 nerve root damage results in difficulty extension at elbow, wrist and fingers;
sensation abnormalities over the middle finger also occur. C7 is important in the
triceps jerk.
Although the fourth and fifth digits are held in the clawed position when the nerve
is injured at the wrist, a high lesion paralyses the long flexors to these two fingers
and results in the loss of this sign. A test for paralysis of the palmar interossei,
supplied by the ulnar nerve, is the inability to adduct the fingers and thus to be
unable to grip a sheet of paper between them.
The femoral nerve may be damaged from fractures of the pelvis or femur, or
dislocations of the hip, and hip or hernia surgery. It can also be involved in psoas
abscesses, thigh wounds and frequently in large psoas haematomas in patients with
haemophilia and diabetic amyotrophy. Partial lesions are common from thigh
wounds with the nerve to the quadriceps most frequently involved and causing
great problems in walking with the knee often giving way, especially when
descending stairs. It leads to a loss of power in the knee extension. In addition
there is quadriceps wasting, loss of knee jerk and impaired sensation over the front
of the thigh.
The inferior alveolar nerve, a branch of the mandibular division of the trigeminal
nerve (V), traverses the inferior alveolar, or dental, canal of the mandible to supply
all the teeth of that hemimandible; all the teeth on that side are therefore
anaesthetised. The mental branch of the nerve emerges through the mental foramen
to supply the lower lip, which becomes numb in a successfully performed block.
The muscles of the tongue, of mastication and of facial expression are not affected.
Although the fourth and fifth digits are held in the clawed position when the nerve
is injured at the wrist, a high lesion paralyses the long flexors to these two fingers
and results in the loss of this sign. A test for paralysis of the palmar interossei,
supplied by the ulnar nerve, is the inability to adduct the fingers and thus to be
unable to grip a sheet of paper between them.
The oculomotor nerve enters the orbit through the superior orbital fissure. It
supplies the inferior oblique, superior rectus, inferior rectus and medial rectus
muscles. It also has a parasympathetic branch to the pupillary ciliary muscle and
levator palpebral superioris. Vascular lesions and aneurysms of the posterior
communicating artery can lead to a complete third nerve paralysis. This results in
ptosis due to paralysis of levator palpebral superioris, a dilated pupil and deviation
of the eye to the down and out position due to unopposed action of superior
oblique and lateral rectus with loss of light reflex due to paralysis of constrictor
pupillae.
Prefrontal lesions result in deficits such as: lack of spontaneity, pathological
inertia, impulsiveness, disinhibition and alteration of the consciousness of the self.
The functions of the prefrontal regions include direction of attention,
discrimination of the importance of stimuli, formation of intent, development of a
plan of action, execution of the action and analysis of the results obtained. More
specifically, the ventral regions are above all responsible for the social and
emotional adjustment of the individual, whereas the dorsolateral regions are more
centered on regulation and integration of the cognitive functions. When prefrontal
lesions occur during childhood, the symptoms seem to demonstrate interference in
the development of introspection, social judgment, empathy, abstract reasoning
and planning. Frontal lesions do not lead to loss of smell directly. Frontal lesions
can lead to enuresis due to lack of inhibition. The same is true for speech problems.
The parietal lobe coordinates spatial orientation.
The oesophagus lies in front of the descending aorta. It extends from the level of
C6 to T10. The thoracic part of the oesophagus lies anterior to the recurrent
laryngeal nerve. It derives its arterial supply from the inferior branch of the
thyrocervical trunk, branches of the thoracic aorta, bronchial arteries and ascending
branches from the left gastric and inferior phrenic artery. Regarding venous
drainage, the upper third is drained by the superior vena cava, the middle third by
the azygos system and the lower third by the portal venous system via the gastric
veins.
The IVC lies to the right of the abdominal aorta. It pierces the diaphragm at the
level of T12 but bifurcates at the level of L4, not L3. 95% of abdominal aortic
aneurysms occur below the level of the renal arteries. Branches of the abdominal
aorta are numerous, and include the suprarenal, renal, gonadal, coeliac axis,
superior and inferior mesenteric vessels, inferior phrenic, lumbar, median sacral
and the common iliac vessels.
The recurrent laryngeal branch of the vagus nerve (X) supplies all the muscles of
the larynx apart from the cricothyroid muscle, which is supplied by the superior
laryngeal branch of the vagus nerve. The recurrent nerve also supplies sensory
fibres to the larynx inferior to the vocal cords. The paralysed cord is seen to lie in
the paralytic position, slightly abducted from the midline, and does not move on
phonation.
A homonymous lesion field defect must be posterior to the optic chiasm (where
lesions typically cause bitemporal field loss, though other patterns can occur).
Because the nerve fibres are reversed in relation to their representation in the
retina, the field defect in temporal lobe lesions tends to affect the superior part of
the visual field and in parietal lesions, the inferior part. Optic tract lesions tend to
affect both aspects.
Occipital lobe lesions also cause homonymous field defects. However, because the
macular fibres project to the occipital poles, which receive a blood supply from the
middle cerebral artery (most of the occipital lobe is supplied by the posterior
cerebral artery), the field loss is often small and there may be macular sparing.




Ethylene glycol poisoning;
Severe hypocalcaemia, particularly in this clinical context, is highly suggestive of
poisoning with ethylene glycol. This is oxidised to various organic acids, including
oxalic acid, which combines with calcium to produce insoluble calcium oxalate:
oxalate crystals are often present in the urine. The only other poison that causes
hypocalcaemia is hydrofluoric acid.
Diabetic retinopathy:
The earliest lesions to be detected in diabetic retinopathy are usually dot
haemorrhages (capillary microaneurysms) and venous dilatation. Hard exudates are
characteristic of diabetic retinopathy but they, and blot haemorrhages, usually
appear later. These three are the components of background retinopathy.
Soft exudates and macular oedema are later, sight-threatening, preproliferative,
changes.
Porphyria
The porphyrias are a group of inherited metabolic diseases in which the
metabolism of porphyrins, the precursors of haem, is disturbed. They are classified
as acute (neurological), in which porphyrin precursors are produced in excess, and
chronic, in which photosensitising porphyrins are produced in excess. Most are
inherited as autosomal-dominant conditions, except for congenital erythropoietic
porphyria (autosomal recessive). Although in some instances porphyria cutanea
tarda is inherited (autosomal dominant), most cases are sporadic, and occur in
patients with liver diseases, especially alcohol-related. The acute porphyrias
include acute intermittent porphyria and variegate porphyria. These are rare genetic
errors of haem biosynthesis. Accumulation of porphyrin precursors
(porphobilinogen and d-aminolaevulinic acid) cause neuronal and visceral crises.
The acute intermittent type is inherited as an autosomal-dominant, although
penetrance is low and around one-third of cases are due to mutations. The urinary
porphobilinogen level is raised during an acute attack, but only 50% of samples
will turn red on standing. Faecal levels of porphyrin are normal in patients with the
acute intermittent type, unlike the variegate form. Variegate porphyria is also
inherited as an autosomal-dominant and is associated with photosensitivity causing
blistering.
In acute intermittent porphyria, a deficiency of porphobilinogen deaminase leads to
the accumulation of porphyrin precursors in acute attacks. These cause
neurological symptoms, particularly autonomic. Abdominal pain, nausea,
vomiting, constipation occur in approximately 90% of patients. Hypertension,
tachycardia and motor neuropathies also occur relatively frequently, but sensory
neuropathies are uncommon. Neuropsychiatric manifestations include depression,
anxiety, fits and psychosis, but the latter is rare.
Diabetes mellitus
The LDL-cholesterol concentration is usually normal or only slightly elevated in
patients with diabetes (unless they have another cause of hypercholesterolaemia)
even though the LDL particles are abnormal, being denser, richer in triglyceride
and thus more atherogenic. HDL-cholesterol is typically low, and triglycerides are
elevated. Achievement of good glycaemic control may reverse these abnormalities
in type-1 diabetes (HDL-cholesterol may even be increased). However, treatment
may ameliorate, but usually does not normalise, the abnormalities in type-2
diabetes.
Night blindness:
Deficiency of ornithine-d-aminotransferase causes atrophy of the choroid and
retina, beginning as a small yellowish spot and increasing to a circular lesion edged
with pigment giving an atypical retinitis pigmentosa appearance. Children present
with myopia and decreased night vision, which progresses to blindness in middle
life. Cataracts also develop but the optic discs, cornea and iris remain normal. A
few patients develop mild proximal muscle weakness. Microscopic abnormalities
of skeletal muscle fibres are found. Magnetic resonance imaging shows changes in
the central nervous system, but the longer term clinical implications are uncertain.

Plasma ornithine values range from 400 to 1000 mmol/l (normal 75 m mol/l) with
high concentrations in cerebrospinal fluid and the aqueous humour. Between 400
and 900 mg/day is excreted with increased amounts of arginine and lysine
(competitive inhibition of reabsorption). The activity of ornithine-d-
aminotransferase is low in liver and skeletal muscle. Most affected patients have
less than 1% of the normal activity in fibroblasts.

Malabsorption
Albumin is degraded by proteases in the gut. However, a
1
-antitrypsin is a plasma
protein that is resistant to degradation by proteases (it is a protease inhibitor) and
its measurement can indicate leakage of plasma proteins into the gut. Faecal
calprotectin is increased in inflammatory bowel disease, only one of several causes
of protein-losing enteropathy. Calmodulin is an intracellular calcium-binding
protein. Elastase is measured as an index of pancreatic function.

Muscle:
The T tubules are a tubular network formed by the invagination of the sarcolemma
of the myocyte. Sarcolemmal calcium channels are located on the T tubules; there
are two main types of channels T and L types. The T (transient) channels do not
interact with conventional calcium-channel blockers. Calcium-channel blockers
interact with the L-type calcium channels. Titin tethers the myosin molecule to the
Z line, and its elasticity explains the stressstrain elastic relation of striated muscle.
It is the largest protein molecule yet described. The thin actin filaments intertwine
and are carried on a heavier tropomyosin molecule that functions as a backbone. At
regular intervals along this structure is a group of three regulatory proteins called
the troponin complex, which is composed of troponin C, troponin I and troponin
M.

These include: syncope on exercise (associated with hypertrophic cardiomyopathy,
arrhythmogenic right ventricular cardiomyopathy, catecholaminergic polymorphic
VT, and long QT syndrome type 1); syncope with loud noise, fright or emotion
(associated with long QT syndrome type 2); syncope when lying down (associated
with long QT syndrome type 3 and Brugada syndrome); family history of sudden
death (associated with all of the above syndromes); and an odd history. The 12-
lead ECG is the most important investigation for recurrent or unexplained syncope.
Pre-excitation, long QT interval, heart block, and ventricular hypertrophy with
repolarisation abnormalities can all be diagnosed from an ECG.
Infective endocarditis;
Patent ductus arteriosus carries a high risk of endocarditis. The other high-risk
lesions are small ventricular septal defects and aortic regurgitation.

Cardiac surgery:
TGA with intact septum is corrected by the switch operation, but TGA VSD PS
will often need a rastelli to connect the right ventricle to the pulmonary artery with
a homograft. Hypoplastic left heart syndrome is palliated with the Norwood
operation at birth, then the cavo-pulmonary shunt at about 6 months and the Fontan
operation at about 3 years. Ross operation is used to remove the regurgitant aortic
valve, replace with the childs own pulmonary valve and to insert a homograft into
the pulmonary position.

Vascular rings:
The 2 most common types of complete vascular rings are double aortic arch and
right aortic arch with left ligamentum arteriosum. These make up 85-95% of the
cases.

Acne ;
First-line therapy for acne involves the use of topical antibiotics such as
tetracyclines, keratolytics or topical retinoids.
Second-line therapy involves a 34 months course of low-dose antibiotics such as
tetracyclines or erythromycin, Dianette (if there is no contraindication), or UVB
phototherapy (although this is rarely used now).
Third-line therapy involves the use of oral retinoids, although these are prescribed
only by specialists in dermatology and carry high risk of teratogenicity.

Naevus;
A feature of the Sturge-Weber syndrome is the presence of a port-wine stain
(capillary angioma) - a benign proliferation of vascular and connective tissue that
may be associated with a developmental defect of mature dermal capillaries.
Histologically, networks of ectatic vessels in the outer dermis are evident. The
lesion is present at birth, is generally unilateral affecting the face, trunk or limbs
and is variable in size. Usually, there is a sharp midline borer on the more common
unilateral lesions. If areas supplied by the maxillary and ophthalmic divisions of
the trigeminal nerve are involved there may be associated angiomas of the
underlying meninges, producing neurological manifestations comprising the
Sturge-Weber syndrome. It arises sporadically. Jacksonian epilepsy, hemisensory
disturbance, hemiplegia, contralateral hemianopia and mental retardation have all
been described. Choroidal angioma, glaucoma, buphthalmos (large eye) are ocular
manifestations. Skull radiography may demonstrate intracranial tramline
calcification.
Histologically, a strawberry naevus is caused by a benign proliferation of
endothelial cells, followed by involution and development of fibrous tissue in the
vascular spaces. It occurs in 1% of children and although it sometimes presents at
birth, it usually appears shortly afterwards. Clinically, it presents as one or more
rapidly growing, dome-shaped, bright-red lumps, most commonly on the head or
neck. The lesions grow for the first 12-15 months of life then gradually and
spontaneously resolve, in most cases disappearing by the age of seven years. The
surface of a lesion may become eroded, crusted or bleed: infection can occur.
Large facial lesions may be associated with coarctation of the aorta, and posterior
fossa abnormalities can sometimes occur. Laser therapy may be useful for
haemangiomas. Tuberose sclerosis is an autosomal-dominant disorder
characterised by hamartomas located throughout the body, often prominently
involving the central nervous system and skin. Two loci on chromosomes 9 and 16
have been identified. The condition has a variable expression and penetrance and is
further characterised by angiofibromas, seizures and mental retardation. Skin
features comprise periungual fibromas, cutaneous angiofibromas (adenoma
sebaceum) producing small and discrete pink papules mainly affecting the centre
of the face, Shagreen patches (collagen naevi) - ie flesh-coloured leathery
thickenings of the skin - and ashleaf-shaped areas of depigmentation that become
more visible under Woods light. The only treatment is symptomatic, ie
anticonvulsants. Neurofibromatosis is another example of a neurocutaneous
syndrome (phacodermatoses). This is an autosomal-dominant disorder
characterised by neurofibromas affecting the nervous system and skin. The gene
responsible is located on chromosome 17 and encodes neurofibromin, which
down-regulates the function of the p21 ras oncoprotein. Lesions include acoustic
neuroma, schwannoma, caf-au-lait spots (hyperpigmented macules), axillary
freckling and cutaneous neurofibromas. Systemic manifestations include
kyphoscoliosis, bone cysts, phaeochromocytoma, acromegaly and mental
deficiency and epilepsy. Type 2 neurofibromatosis is a different entity: there is a
propensity in this disease for the development of VIIIth nerve schwannomas or
meningiomas.
Erythema multiforme:
Infections:
Bacterial (including Bacille Calmette-Gurin (BCG) vaccination, hemolytic
streptococci, legionellosis, leprosy, Neisseria meningitidis, Mycobacterium,
pneumococcus, Salmonella species, Staphylococcus species, tuberculosis,
Mycoplasma pneumoniae),Chlamydial,
Fungal
Parasitic (Trichomonas species, Toxoplasma gondii),
Viral (especially herpes simplex).
Drugs: Antibiotics (including, sulfonamides), anticonvulsants, aspirin,
antituberculoids and many others.

Physical factors - Radiotherapy, cold, sunlight

Others - Collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia,
multiple myeloma, myeloid metaplasia, polycythemia
EM minor is regarded as being triggered by HSV in nearly 100% of cases. A
herpetic etiology also accounts for 55% of cases of EM major. Among the other
infections, Mycoplasma infection appears to be a common cause.

Lichen planus:
Lichen planus is an intensely pruritic eruption of unknown aetiology. It has a very
characteristic clinical appearance, composed of grouped, small and shiny, flat-
topped violaceous papules with an overlying network of fine white lines
(Wickhams striae). The usual distribution involves the flexor aspects of the knees,
elbows, ankles and wrists, with the mouth being more commonly affected. Lichen
planus exhibits Koebner's phenomenon, in which lesions tend to occur at the sites
of trauma. This is also the case for vitiligo, psoriasis and plane warts. The disease
tends to remit spontaneously between six months and two years. Although topical
steroids and antihistamines are helpful for symptomatic relief, often no treatment is
required in mild cases. Fading skin papules leave postinflammatory
hyperpigmentation, while scalp involvement may produce a scarring alopecia.
Pityriasis rosea:
The first clinical lesion to appear in pityriasis rosea is the so-called herald patch,
an isolated erythematous patch, appearing on the trunk, surrounded by a ring of
scaling skin. A number of oval macules appear on the upper arms, remainder of the
trunk and upper thighs some 24 days later. Involvement of the hands, feet or scalp
is rare. Severe itching is uncommon. Pityriasis rosea normally remits within 48
weeks. Cases occur with increasing frequency in spring and autumn, suggesting a
possible viral aetiology.

Systemic antihistamines or calamine lotion may be useful to relieve itching.
Topical steroids do not shorten the duration of the disease, and systemic steroids
have no value in disease modification.

Puberty:
Breast-bud enlargement is the first sign of puberty in girls. This begins between the
ages of 9 and 12 years and continues to 1218 years. Pubic hair growth occurs
next, at ages 914 years, and is complete at 1216 years. Menarche occurs
relatively late (age 1115 years). Peak height velocity is reached earlier (1013
years) and growth is completed much earlier than in boys.
Precocious puberty:
Hypogonadism is a common feature in gigantism, leading to delayed epiphyseal
closure and thus a more prolonged growth period.

Precocious puberty is classified into two types:
1) True precocious puberty, caused by premature secretion of gonadotrophins,
which stimulate the production of testicular androgens and sperm. This results in
virilisation and an increase in testicular size. Causes include:
idiopathic precocious puberty
central nervous system lesions which affect the posterior hypothalamus, eg.
craniopharyngioma, haematoma, hydrocephalus, neurofibroma, tuberous
sclerosis, postencephalitic lesions
hCG-secreting tumours, eg. hepatoblastoma
primary hypothryoidism, probably due to direct stimulation of FSH
receptors by the high circulating levels of serum TSH; testicular
enlargement and other features regress with thyroxine therapy.
2) Precocious pseudopuberty results from secretion of androgens from the adrenal
gland or testes. Excessive androgens result in virilisation, but sperm production is
not stimulated and the testes remain small. Causes include:
adrenocortical hyperfunction (congenital adrenal hyperplasia, virilising
adrenocortical tumours)
Leydig cell tumour
McCune-Albright syndrome (hyperpigmentation, polyostotic fibrous
dysplasia, multinodular goitre and other glandular hyperfunction).
The growth spurt at puberty is brought about by the secretion of androgens in the
male and oestrogens in the female. However, it is oestrogens that ultimately
terminate growth by causing the epiphyses in the long bones to fuse. Thus
oestrogens rather than androgens are responsible for skeletal maturation,
epiphyseal fusion and cessation of growth in males and females. All the other
hormones are involved in growth alone.
In type-4 renal tubular acidosis, metabolic acidosis occurs coupled with a low
plasma bicarbonate level and hyperchloraemia.
Gordons syndrome is associated with the renal retention of sodium, causing
hypertension, volume expansion, low renin/aldosterone, hyperkalaemia and
metabolic acidosis.
Decreased sodium and increased potassium levels are seen in patients with
pseudohypoaldosteronism.

Type 1 DM is associated with HLA DR3 and DR4. The majority of patients have
demonstrable islet cell antibodies at diagnosis. The incidence of DM in the normal
population is 0.4%, with the risk to siblings being 6%. HLA identical siblings have
a risk of 12%. Twin studies suggest that one third of the susceptibility is genetic.

Hyperphosphatasia is an inborn error of metabolism leading to a deficiency
of alkaline phosphatase (ALP).


Extraintestinal manifestation of Crohns disease includes oral aphthous ulcer,
erythema nodosum, osteomalacia, and anaemia due to chronic malabsorption;
osteonecrosis due to chronic steroid therapy; gallstone formation due to ileal
involvement of disease leading to poor bile salt reabsorption; oxalate kidney stones
due to colonic disease; pancreatitis due to sulfasalazine, mesalamine, azathioprine,
or 6-mercaptopurine therapy; bacteria overgrowth due to surgical resection; and
miscellaneous manifestations such as amyloidosis, thromboembolic complications,
hepatobiliary disease, and primary sclerosing cholangitis.
Coeliac disease:
Coeliac disease may present with growth failure with delayed puberty in the
absence of diarrhoea. The prevalence of this complication has fallen however
following earlier diagnosis and management. Modes of presentation include the
classical presentation in the child between 9-18 months of age with diarrhoea,
misery, and failure to thrive, presentation in the older child with short stature,
delayed puberty, and iron resistant anaemia in the absence of diarrhoea, silent
coeliac disease in which the pathognomonic small intestinal biopsy is present in an
apparently well individual with no symptoms, and latent coeliac disease in which
the serological markers of coeliac disease are positive and the intestinal biopsy still
normal.
Hyposplenism and splenic atrophy occurs in up to 50% of adults with coeliac
disease, but is rare in children.
Malabsorption:
Carbohydrate malabsorption: Pancreatic insufficiency (eg CF), absence or
reduction of the brush border disaccharidases after an infection in the intestine,
congenital sucrase, isomaltase and lactase deficiency, bacterial overgrowth.
Fat malabsorption: Exocrine pancreatic insufficiency is the principal condition
resulting in severe fat malabsorption (Pancreatitis, pancreatic resection, cystic
fibrosis, Schwachmann-Diamond syndrome, Johnson-Blizzard syndrome, and
Pearson syndrome). Significant obstructive biliary or cholestatic liver disease or
extensive intestinal mucosal disease, such as occurs in celiac disease, may also
result in severe steatorrhea. Bacterial overgrowth in the small bowel deconjugates
bile acids, thereby inactivating their ability to help lipids form a micelle.
Protein malabsorption: exocrine pancreatic enzyme deficiency, congenital
enterokinase. Protein-losing enteropathy is often caused by the leakage of protein
from the serum due to inflammation of the mucosa, as in Crohn disease and protein
sensitivity syndromes.
Vitamin malabsorption: Malabsorption of vitamin B-12 and folate is associated
with tropical spruce. Intrinsic factor deficiency resulting from atrophic gastritis or
absence (from resection) or disease of the terminal ileum (the predominant site of
active B-12) results in vitamin B-12 malabsorption.


Fetal sexing at 17 weeks may be done by ultrasound,

Noonan syndrome:
Noonan syndrome is a common autosomal dominant condition, caused by
mutations in PTPN11 on chromosome 12q. The incidence is around 1 in 2500
individuals. Affected individuals are characteristically short (mean height
around 3rd centile), and have down slanting palpebral fissures, with heavy or
hooded eyelids. A low posterior neckline and short webbed neck are often
seen.
50-80% of individuals with Noonan syndrome have a cardiac defect. The most
common defect is pulmonary stenosis. Hypertrophic cardiomyopathy occurs in
about 20% of individuals with Noonan syndrome, and may present throughout
life. Feeding problems in infancy are very common, and this appears to
correlate with mild developmental delay (seen in about 30% of cases). It is a
collection of features including short stature, broad forehead with hypertelorism,
downward sloping palpepral fissures, partial bilateral ptosis, neck webbing, low
posterior hairline, micrognathia, high-arched palate, shield chest, widely spaced
nipples, kyphoscoliosis, renal anomalies, bleeding problems and reduced IQ.
Noonans syndrome is associated with cardiac anomalies including pulmonary valve
stenosis, peripheral pulmonary artery stenosis, and ASD.

WiskottAldrich syndrome.
The thymus may be hypoplastic giving an impaired cellular immunity and IgM
levels are low, while IgA and IgE may be raised. The WASP protein is
expressed in cells of all haematopoietic lineages. It may serve a cytoskeletal
organising role for signalling elements that are particularly important in
platelets and T cells. The immunological defects include low serum
concentrations of IgM, while IgA and IgG are normal and IgE is frequently
increased. The number and class distribution of B lymphocytes are usually
normal.


Haemoglobinopathy:
It is important to realise that a2b2 chains are not produced until after birth,
wheras Alpha chains contribute to haemoglobin before birth.

The a globin gene cluster is located on chromosome 16 and the b globin gene
cluster is located on chromosome 11. The a genes are duplicated on each
chromosome 16 and therefore we inherit two a genes from each parent. The b
genes are not duplicated and we inherit one from each parent.

Sideroblastic anemia:
Sideroblastic anaemias are characterised by erythroid hyperplasia and the
presence of ringed sideroblasts in the bone marrow. In the hereditary form the
anaemia is hypochromic and microcytic and is due to deficiency of the enzyme
delta-aminolevulinic acid synthetase (ALA synthetase). This form occurs in
males and is transmitted by females in an X-linked fashion, but it also rarely
occurs in females who are double hemizygotes. In patients with the hereditary
type, the degree of anaemia is not severe and regular phlebotomy is necessary to
counteract the problems of tissue iron overload which occur in these patients.
Iron chelation may also be necessary in some cases especially where blood
transfusion proves necessary.

The primary acquired form, which occurs in either sex mainly in middle and old
age, is due to a somatic mutation of the red cell progenitor cells causing defects
in both heme synthesis and defects in DNA synthesis. It is now classified with
the myelodysplastic syndromes. Very rare cases do occur in children.

Some patients respond to pyridoxine therapy.

Factor VIII is a co-factor. It is activated by Thrombin and mediates the
conversion of X to XA. Its half life in circulation is some 12 hours (in contrast
to Factor IX that has a half life of 24 hours). When given therapeutically
therefore, it needs to be given twice daily in contrast to Factor IX, which can be
given daily.
In Type II von Willebrands disease the von Willebrands protein is present
although its function is reduced. Therefore, the antigen level is higher than the
ristocetin co-factor activity level. In Type 2B there is also thrombocytopenia.

In Type 3 there is a very severe quantitative deficiency. This is autosomal
recessive. This presents as Haemophilia A does but also with the mucosal and
skin bleeding typical of von Willebrands disease.

Treatment: In Type I there may be no need for any treatment or DDAVP may
be used as this increases production of von Willebrand antigen. In type 2 a
concentrate may be required of von Willebrand protein (this is plasma derived
and is not a recombinant product). Fresh frozen plasma will require very little
von Willebrand protein and litres will be required for a correction of bleeding
diathesis. In Type 3 again concentrates are required

Complement system:
The pathway may be activated in a classic way, by antigenantibody immune
complexes, apoptotic cells, C-reactive protein (CRP) bound to ligand, and
certain viruses and bacteria, or in an alternative way by bacterial endotoxin,
fungal cell walls, viruses, and certain tumour cells. Deficiencies of C3, C1q or
factors H or I lead to increased susceptibility to infection with capsulated
bacteria.
Complement perforates invading bacteria, dilates blood vessels, stimulates
histamine release and attracts neutrophils.


Hyper IgM syn:
Hyper-IgM syndrome, or CD40 ligand deficiency, is an X-linked condition
presenting in a similar way to X-linked agammaglobulinaemia with recurrent
sinpulmonary disease. Levels of IgG, IgA and IgE are undetectable, but there
are normal or high levels of IgM and IgD. This is due to the role of CD40 in B-
cell maturation and isotype switching. This is a T-cell defect and affected
individuals are also susceptible to P. jiroveci pneumonia. They can develop
chronic cryptosporidial infection, leading to sclerosing cholangitis and liver
failure. They have an increased risk of malignancy, particularly abdominal
cancers.

B cells have surface IgG and MHC class II, undergo somatic hypermutation and
isotype switching (ie switching through the immunoglobulin classes). Plasma
cells are fully differentiated cells from B cells, and hence lack these features.

IL-4: involved in proliferation of B cells , and the development of T cells and
mast cells . Important role in allergic responses.
IL-8: Neutrophil chemotaxis
IL-1 cause inflammation and fever, Ig production and phagocyte activation. IL-
6 & TNF are different groups of cytokines and although they act synergistically
to stimulate T cells IL-6 cause thrombopoiesis and TNF cause vascular
thrombosis and tumour necrosis.
C3b acts as an opsonizer.
C5a is an anaphylatoxin, causing the release of histamine from mast cells; It is
also an effective leucocyte chemoattractants, causing the accumulation of white
blood cells, especially neutrophil granulocytes, at sites of complement
activation.

Pneumococcal conjugate vaccine was recommended for children under 5 years
with chronic lung, renal, liver and cardiac conditions, diabetes,
immunosuppresion / immunocompromised, cochlear implants, CSF shunts and
previous invasive pneumococcal disease.

GBS:
About 25% of mothers in the UK are carriers, and the incidence of proven
neonatal disease is about 0.7/1000 live births. Late onset GBS infection (after 1
week of age) is well described and accounts for about one-third of all cases.

Immunisation of the immunocompromised
Significant contact with an individual with chickenpox (play or direct contact
for more than 15 minutes, on ward or in household), during the infectious
period from 2 days prior to onset of rash, until crusting of all vesicles, or with
herpes zoster (direct contact with exposed lesions only) requires one of the
following prophylactic treatments in varicella antibody negative patients:


Malaria;
Hepatic hypnozoites are only seen with P. vivax and P. ovale, not P.falciparum.
Malarial parasites (trophozoites, schizonts or gametocytes) are identified
morphologically on a peripheral blood smear. Thick smears are used to identify
the presence of parasites. The percentage of parasitized erythrocytes can then
be assessed on a thin film (>2% is considered severe).
Where only P. vivax malaria exists, prophylaxis should be chloroquine or
proguanil (Paludrine). Where P. falciparum exists and is sensitive to
chloroquine, this should be used. Where chloroquine-resistant P. falciparum
exists, chemoprophylaxis should be by mefloquine although this is not advised
for young children, for whom chloroquine plus proguanil should be used.

Hypercalciuria, or excessive urinary calcium excretion, is the most common
identifiable cause of calcium kidney stone disease. The most common types of
clinically significant hypercalciuria are absorptive, renal leak, resorptive, and
renal phosphate leak. Other causes of hypercalciuria that need to be considered
include hyperthyroidism, renal tubular acidosis, sarcoidosis and other
granulomatous diseases, vitamin D intoxication, glucocorticoid excess, Pagets
disease, Albright tubular acidosis, various paraneoplastic syndromes, prolonged
immobilisation, induced hypophosphatemic states, multiple myeloma,
lymphoma, leukaemia, metastatic tumors especially to bone, Addison disease,
and milk-alkali syndrome.

Conduct disorder:
Multisystemic therapy (MST) is found to be effective in children with conduct disorder.
In MST, Problem behaviours are conceptualised as being linked with individual
characteristics and with various aspects of the multiple systems in which the adolescent
is embedded, including the family, peers, schools, and neighbourhood.
Pericardial effusion is a specific complication to watch out for after ASD repair. Chest
pain radiating to the left shoulder is a classical history. Children can look well despite
having significant effusions.

Other complications of cardiac surgery include:
Arrhythmias
Ischaemia
Surgical closure of VSDs is the commonest bypass operation performed in infancy

VACTERL association :VSD
Cornelia de Lange :ASD, VSD
Phenytoin : Aortic stenosis, Pulmonary stenosis, Co arctation of aorta
The tests for vision at the various age groups are given below:
Age Test
4 weeks Visual-evoked potentials
6 weeks Optokinetic nystagmus
3 months Follows objects 90 cm away through 180
0

10 months Identifies and picks up small objects
23 years Identification of miniature toys at 3 m
34 years Stycar letter matching tests at 3 m distance
5 years Snellen charts

The hearing tests appropriate for the various age groups are listed below;
Birth - 6
months
otoacoustic emissions; brainstem-evoked potentials; auditory
response cradle
6 - 9 months distraction test
2 - 3 years speech discrimination test
3 - 5 years threshold audiometry


The danger signs of a global delay in development are:
parental concern
no social smile at 2 months
not achieved good eye contact at 3 months
not reaching for objects at 5 months
failed distraction test at 8 months
not sitting with support at 9 months
not walking unaided at 18 months
not saying single words with meaning at 18 months
regression of acquired skills
discordance in developmental areas.
The milestones on speech are:
vocal turn taking 3 months
intonated babble 6 months
protowords 9 months
few meaningful words 12 months
many words, points to many objects 18 months
many words, telegraphic speech (two-word sentences), names objects 2 years
three-word sentences, tells name age and sex, counts to 10 3 years
likes rhymes, tells stories, tells full name and address 4 years
fluent speech, tells name age address and birthday 5 years
Birth Startled by a loud noise
1 month Notices prolonged white noise like that of vacuum cleaner
4 months Quietens at caregivers voice
7 months Turns head to sound
1 year Responds to name, no and bye-bye
By 8 months an infant should be able to transfer objects. Reaching for objects, grasping
them and mouthing is achieved at around six months.
The Gross motor milestones achieved by 2 years of age are:
run safely
walk into a large ball while trying to kick
push and pull large wheeled toys
walk up and down stairs 2 ft per step.
The Fine motor milestones achieved by 4 years of age arebuilding a tower of 10 or more
cubes and three steps using six cubes, draw a person with head legs and body, draw a cross,
thread small beads, copy letters O, X, V, T, H and approximating thumb with each
finger.
The fine motor skills at five years of age are copying a square, threading a large-eyed
needle, counting fingers of one hand using index finger of other hand and drawing a
person with head, body, legs, eyes, mouth, and nose. Most children will be able to copy a
circle and a cross by age 3
1
/
2
to 4 years. The median age for independently copying a
square is 5 years, but many will be able to perform this a year or so earlier if the task is
demonstrated by the examiner. Most children will copy a triangle by age 5
1
/
2
.
Kicking a ball well, building a tower of 10 blocks and using simple scissors are tasks
expected of most 3-year-olds. Most 4-year-olds are able to hop briefly on their
'preferred' foot, but by 5 years are expected to hop forward for several hops on either
foot.


Hypomelanosis of Ito
Hypomelanosis of Ito is a rare disorder of localised hypopigmentation that is not
inherited. The melanocytes in these areas are deficient in melanin and also smaller than
expected. Unlike incontinentia pigmenti, the hypopigmented areas are present from
birth and do not undergo any changes. They appear as well-defined streaks and whorls
following the lines of Blaschko. There are associated seizures, learning problems,
microcephaly, scoliosis, abnormal limbs, eye defects and congenital heart disease.

Type 1 MEN is associated with
parathyroid adenomas/ hyperplasia
pancreatic islet cell tumours
adrenal cortical non-functioning tumours
thyroid follicular cell adenomas
anterior pituitary adenomas
Pinpoint pupils suggest narcotic or organophosphate poisoning or a metabolic
condition. Small reactive pupils may be caused by a metabolic disorder or a medullary
lesion. A mid-brain lesion causes fixed mid-size pupils. Fixed dilated pupils can be
found in hypothermia, hypoxia, during a seizure or afterwards, anticholinergic
ingestion or as a late sign in barbiturate ingestion. If only one of the pupils is dilated,
epilepsy, 3rd cranial nerve palsy, tentorial herniation or an intracranial disorder should
be considered.
Familial Mediterranean fever (FMF) has an incidence of approximately 1 : 1000 in the
Turkish population. It presents less than 10 years of age in 5060% of patients. The
fever is present for 48 to 96 h, however is often worse in the first 12 h. Abdominal pain
is present in most attacks unless mild and joint symptoms are also very common.
Erysipelas-like rash is commonly present especially below the legs. Routine blood tests
tend to be unhelpful although C-reactive protein (CRP) and erythrocyte sedimentation
rate (ESR) can be elevated. A rapid test has been developed for the most common
mutations of the MEFV gene. A sub-mucosal rectal biopsy can be performed to look for
amyloidosis. Amyloidosis is the long-term complication, which leads to death. The
treatment of choice is colchicine is so effective in preventing attacks of FMF that it
prevents the development of amyloidosis. The most important aspects of medical care
are to make the correct diagnosis and to institute therapy.

Toxic megacolon is a medical emergency and occurs in approximately 5% of severe
attacks of ulcerative colitis. It can also be associated with Crohns colitis, ischaemic
colitis, pseudomembranous colitis or amoebiasis. Diagnostic criteria include
radiographic evidence of dilated (> 6cm) transverse colon, and at least three of the
following: fever > 38 C, heart rate (HR) > 120/min, neutrophilia > 10.5, anaemia.
Management is supportive, involving giving intravenous fluids and blood, giving
nutritional support, avoiding antidiarrhoeal drugs and opioid analgesics, giving
intravenous antibiotics, rolling manoeuvre into prone or knee-elbow position to aid
evacuation of gas per rectum, and inserting a nasogastric tube to aspirate bowel gas and
fluids. If there is no improvement within 24 to 48 hours, immediate surgery is indicated.
Urinary tract infection:
Renal tract ultrasound during acute admission and DMSA scan at 4-6 months
The NICE recommendations have drawn attention to the poor evidence-base for the
case that a) childhood UTIs contribute significantly to the development of end-stage
renal failure or chronic renal disease, or that b) proven interventions exist to modify
this risk. Recommendations for imaging after a first uncomplicated UTI in children
over 3 years of age have been withdrawn, and imaging recommendations for younger
children have been significantly scaled down. In children < 3 years at first infection
imaging recommendations are based on the presence or absence of atypical features in
the acute presentation which raise the possibility of renal tract obstruction, or signify a
higher risk of later renal scarring. These features include infants who are sick (or
bacteraemic) at presentation, whose illnesses resolve slowly (>48 hrs), and who have
non-E.coli isolates. Appropriate imaging investigations for children with atypical UTI
who are aged over 6 months but younger than 3 years should include an ultrasound
scan before discharge from hospital and a DMSA scan performed after acute
parenchymal changes are likely to have resolved (usually at least 4 months after
infection). Recommendations for an MCUG are restricted to infants under 6 months of
age with recurrent or atypical infection, or for children who have clinical or imaging
findings to suggest an appreciable risk of vesico-ureteric reflux.
The recommendations did not however change advice that urine should continue to be
sent for urgent microscopy and culture in ill or febrile children (i.e. with suspected
upper tract involvement) and in all children under the age of 3 years. Initial tests
(providing results at the bedside or within a few hours) have an important place in
diagnosis, both in directing immediate management and where there is uncertainty
about the influence of contamination on urine culture results. Of the listed alternatives,
urine microscopy for white cells ('pyuria') performs best in suggesting the presence of
infection, although no tests perform particularly well in excluding this possibility. In
older children the combination of positive tests for both leukocyte esterase and nitrite
are thought to perform well-enough to be used as first-line tests in children over the age
of 3 with no previous history of urine infection. This new recommendation aims to
facilitate (and so encourage) urine testing in primary care and when urgent microscopy
and/or culture are not readily available. Most infecting coliforms are able to convert
dietary nitrate to nitrite in the bladder, but tests based on the presence of urinary nitrite
may be negative in younger infants and in children with urinary frequency/bladder
instability, where there is reduced bladder dwell-time. Nitrite testing will always be
('falsely') negative in infection with pseudomonads or Gram-positive organisms such as
enterococci and Staphylococcus saprophyticus. Dipstick tests for leukocyte esterase
similarly have inadequate sensitivity when used alone to detect UTI in young children.
Debates about appropriate methods of urine collection in infants and children in
nappies will continue to be conducted with vigour, but the NICE recommendations
acknowledge that clean catch specimens may sometimes be difficult to obtain and
suggest urine collection pads and bags as acceptable (but second and third-line)
methods of sample collection. SPA and CSU are moderately invasive but justified in
sick infants where prompt antibiotic administration is felt to be imperative. In practice,
a combination of dipstick, microscopy and culture results are collated in arriving at a
final diagnosis, and the availability of a second urine sample (taken ideally before
antibiotics are started) is often helpful in these deliberations.


DMD:
PCR is specific in confirming the carrier status. Other tests are not needed. This will
help in planning prenatal diagnosis for the next pregnancy. After confirming mothers
carrier status by molecular methods, other female members in maternal side also may
be tested by molecular methods for carrier status to enable counselling and plan
prenatal diagnosis where necessary or reassure that they are not carriers. DNA
diagnosis is confirmative in 85% of cases of DMD. Mother is to be tested only after
confirming diagnosis in the child. Muscle biopsy is required only when DNA testing is
not informative, in small%age of cases.


Definitions of obesity in paediatrics include:

Body mass index above the 95th centile
Weight more than 20% greater than median weight for height
Triceps skin fold thickness above the 85th centile
Weight for height above the 95th centile

Diamond blackfan syn:
This is an autsomal dominant inherited steroid responsive hypoplastic anaemia.
Erythropoietin levels are elevated. Dysmorphic features are seen including webbing of
neck, short stature, cleft palate, and anomalies of the thumb. Congenital heart disease is
also present in one-third of the patients. Severe anaemia in infancy is not a feature of
Turners syndrome and Russell-Silvers syndrome. TEC is also associated with
reticulocytopenia, but has a later onset around 12 months of age. The MCV and HbF
levels are normal and the anaemia does not respond to prednisolone.
Iron studies in microcytic anaemia can help differentiate causes:
SERUM IRON TIBC
%
TRANSFERRIN
SATURATION
FERRITIN
IRON DEFICIENCY Low High Approx. 10 Low
CHRONIC DISEASE Low Low Normal Normal/increased
BETATHALASSAEMIA Normal/increased Normal Normal Normal
SIDEROBLASTIC - Increased Increased Approx. 100 Increased

Iron deficiency anaemia is associated with low serum iron and consequently a high total
iron binding capacity, so resulting in a decrease in the transferrin saturation (A) and
serum soluble transferrin receptors. The zinc protoporphyrin/haeme ratio is increased
and serum ferritin levels are decreased. Iron deficiency progresses from a decrease in
serum ferritin. (Earliest) => decrease in transferrin saturation => increase in
erythrocyte porphyrin => decrease in mean cell volume (MCV) => decrease in
haemoglobin.(Last)
Diamond-Blackfan syndrome is red cell aplasia that presents in the first year with
anaemia and clinical features that may include cleft lip, web neck and triphalangeal
thumb.

Diamond-Swachmann syndrome is characterised by pancreatic insufficiency,
neutropenia (anaemia and thrombocytopaenia can also be present), gingivitis,
hepatomegaly, renal tubular dysfunction and metaphyseal achondroplasia.