Lysosomal Storage Disorders

Hope | Believe | Achieve
Govind | Pompe disease | India
Lysosomal Storage Disorders

- Diagnosis & Management
ZIN.CERZ.16.05.0012
INTERNAL USE ONLY
From 1st patient in the world…
…..1st patient in India
1983 1991 2001 2011
GZIN.CERZ.16.05.0012
1998
1983 2004 1991 2010 NOW
2001
INTERNAL USE ONLY
15 Years Journey of Gaucher Patient
INTERNAL USE ONLY
Our Strength: Our Patients
INTERNAL USE ONLY
What are Lysosomal Storage Disorders (LSDs)?

• Family of > 50 genetic disorders1
• Monogenic autosomal or X linked diseases
• Progressive diseases
• Etio-pathogenetic mechanism:
Specific Gene mutation → specific enzyme deficiency → defective

lysosomal acid hydrolysis of endogenous macromolecule → progressive
accumulation of macromolecule in lysosomes → lysosomes become
engorged1 → structural and biochemical changes secondary to storage
→ irreversible organ damage2
1. Meikle P et al. JAMA. 1999;281:249-254.
2. Wraith JE et al. J Pediatr. 2004;144:581-588.
INTERNAL USE ONLY

LSDs Result Due to Enzyme Deficiency
• Caused by Inherited enzyme deficiencies that result in

an accumulation of substrate in the lysosome organelles.
− Waste products accumulate in the lysosomes of cells, which leads to
disruption of cell function
• Severity generally varies with the degree of protein deficiency.

− The most severe deficiencies cause death in early childhood while
milder deficiencies may not present clinically until adulthood.
• Diverse clinical manifestations, the infrequent occurrence, and the
variation in severity make early diagnosis of these diseases extremely
difficult.
INTERNAL USE ONLY
History of LSDs
• 1881: First description of Tay-Sachs disease.
• 1882: First description of Gaucher disease
• 1955: Lysosome discovered by Christian De Duve
• 1963: The ﬁrst demonstration of a link between an enzyme deﬁciency and a storage
disorder (Pompe’s disease) →paved the way for LSDs.
• 1970s : Many more LSDs described
• 1990: 1st successful treatment (Gaucher’s disease with b-glucosidase)
Gaucher cell 1882
Christian René, viscount de Duve
(1917-2013)
Phillip Ernest GAUCHER

(1854-1919) INTERNAL USE ONLY
LSDs are extremely ‘Rare’
• Overall, LSDs affect 1 in about every 7,700 babies born.
• Individually, however, each of the diseases is considerably rarer,

ranging from about 1 in 57,000 for the most common (Gaucher
disease) to about 1 in 4.2 million for the rarest (sialidosis).
• Because of these diseases’ relative rarity, it can be difficult to find

useful educational information about them.
INTERNAL USE ONLY
LSDs (based on neonatal screening)
Sandhoff 2% Gaucher
14%
Gm1 Gangliosidosis 2%
Mucolipidosis II/III 2%
Niemann Pick A/B 3%
Maroteaux-Lamy 3% MPS I
9%
Niemann Pick C
4%
Sanfilippo B
4% Metachromatic
Tay-Sachs Leukodystrophy
4% 8%
Cystinosis
4% Sanfilippo A
Morquio 7%
5%
Pompe Fabry
5% Krabbe Hunter 7%
5% 6%
INTERNAL USE ONLY

(Adapted from: Meikle et al (1999) Prevalence of Lysosomal Storage Disorders. JAMA, Jan., 1999. Vol. 281,No.3
LSDs are progressive diseases
Clinical status
Clinical
disease
Irreversible Organ
failure
Reversible Tissue
involvement
Sub-clinical
disease
Substrate storage
TIME
INTERNAL USE ONLY
There is a Need for Timely Diagnosis
• Progressive, life-threatening , multisystemic diseases

• Diagnosis frequently delayed or missed
− often (multiple) doctor delay of 5 to 20 years
− often not made at all (despite severe complications)
• Treatment is available for several LSDs
INTERNAL USE ONLY
Some Treatable LSDs
Gaucher Disease - Cerezyme

Pompe Disease - Myozyme
Fabry Disease - Fabrazyme
MPS
 I - Aldurazyme
 II - Elaprase
 IV - Vimzim
 VI - Naglazyme
INTERNAL USE ONLY
LSD : Red Flags in clinical practice
• Unusual facial features (sometimes with enlarged

tongue) (MPS)
• Cloudy appearance to the eyes (MPS/Fabry)
• Purplish-blue skin rash (Fabry)
• Distended belly or protrusions from the abdomen
(that could indicate enlarged organs or hernias)
(Gaucher/ Niemann Pick)
• Short stature, failure to grow/develop properly,
skeletal deformities (MPS)
• Muscle weakness or lack of control, decline in motor
skills or other development (Pompe)
INTERNAL USE ONLY
GAUCHER DISEASE
INTERNAL USE ONLY
Gaucher Disease
• Most common lysosomal storage disorder
• Overall population prevalence of GD type1 ~1:100,000
• Autosomal recessive inheritance (chromosome 1)
• Glucocerebrosidase enzyme activity is deficient
• Engorged macrophages (Gaucher cells)
• Progressive, chronic, heterogeneous, multisystemic,
debilitating, and sometimes life-threatening
Ceramide
Glucocerebroside
+
Glucocerebrosidase Glucose
INTERNAL USE ONLY

Pathogenesis of Gaucher Disease

• Mutations in the acid β-glucosidase gene cause a deficiency of acid β-
glucosidase (glucocerebrosidase), an enzyme that helps to break down
glucosylceramide.
• Glucosylceramide accumulates in the lysosomes of certain cells,
primarily tissue macrophages.
Bone Spleen
Bone Macrophages
Tissue
Marrow Macrophages
Lung
Liver Alveolar
Bone Macrophages
Kupffer Cells
Osteoclasts
INTERNAL USE ONLY

Beutler E, Grabowski GA, Gaucher Disease. Available at: http://www.ommbid.com/
Gaucher Disease Phenotypes

TYPE 1 TYPE 2 TYPE 3
NON- ACUTE CHRONIC
NEURONOPATHIC NEURONOPATHIC NEURONOPATHIC
1/50,000 (pan-ethnic) 1/100,000 1/100,000

Prevalence
1/500 (Ashkenazi Jews) (pan-ethnic) (pan-ethnic)
Age at
Any Infancy Childhood
presentation
Lifespan 6 to > 80 y ~2y 2 to 60 y
Primary CNS
none severe mild to severe
disease
Visceromegaly mild to severe moderate to severe mild to severe
Hematologic
mild to severe severe mild to severe
abnormalities
Skeletal
none to severe none none to severe
abnormalities
Distinguishing between types 1 and 3 in children can be difficult, as CNS symptoms may be subtle in younger patients.
INTERNAL USE ONLY

Meikle PJ et al, JAMA 1999;281:249. Poorthuis BJet al. Hum Genet 1999;105:151.
Gaucher Disease: Clinical Presentation
Non-neuronopathic
Acute Neuronopathic Chronic Neuronopathic
(Type 1)
(Type 2) (Type 3)
Most common
INTERNAL USE ONLY

Gaucher disease: Presentation in Children
Children or adolescents with GD Type 1 often have marked splenomegaly, easy

bruising/bleeding and slower than normal growth and pubertal development.
Growth retardation:
Bone pain (27%) • <5th percentile, 28%
• 5th to 25th percentile, 28%
Hepatomegaly (87%)
Splenomegaly (95%) Osteopenia (20%)
Anemia (40%)
Thrombocytopenia (50%) Erlenmeyer flask deformity
(49%)
Bone marrow infiltration (38%)
INTERNAL USE ONLY

Kaplan P, Andersson HC, Kacena KA, Yee JD, Arch Pediatr Adolesc Med 2006;160:603.
Multisystem Involvement / Bone
Osteo- Pathological
necrosis fracture
Collapsed Bone
vertebrae thinning
INTERNAL USE ONLY

Delays in Diagnosing GD
• Diagnosis is often delayed, especially in GD type 1

− Delay of 4 -10 years between begin of symptoms and diagnosis
− Patients consulted an average of 8 physicians;
− Hematologists were contacted at some point prior to diagnosis by 86
% of all patients
• Presumptive diagnosis can be based on

− Enlarged spleen with low hemoglobin and platelet count
− Bone pain or pathologic fracture with hematologic abnormalities or
organomegaly
INTERNAL USE ONLY
Mistry PK, Sadan S, Yang R, Yee J, Yang M, Am J Hematol 2007;82:697.
Diagnosing GD: Why is GD missed?

Differential Diagnosis—Hematologic Diseases
GD 1 CML ALL NHL MM ITP
Typical age at 2-3 (children)

0-80+ 63 10 70 30-40
diagnosis > 65 (adults)
Bone pain     
Bruising/
     
bleeding
Fatigue      
Less
Hepatomegaly     Rare
common
Less
Splenomegaly     Rare
common
Pseudo- Pseudo- Pseudo-
Gaucher cells In Pseudo-
Gaucher Gaucher Gaucher No
on biopsy clusters Gaucher cells
cells cells cells
INTERNAL USE ONLY  Yes Sometimes

de Fost M et al. Neth J Med 2003;61:3-8.
Treatment Options for Gaucher
Symptom-based Disease-specific
Interventions Therapy
(e.g., supportive care for pain, (enzyme replacement with

orthopedic procedures, Cerezyme®, substrate reduction
bisphsophonates, iron therapy)
supplementation)
Optimal care involves both supportive and disease-specific treatment and
regular follow up with a multidisciplinary team experienced in the
management of Gaucher
INTERNAL USE ONLY

Treatment and Monitoring
Manufacture of Recombinant
Glucocerebrosidase: Cerezyme
Bacterial DNA Bacterium
Plasmid
Culture Medium
Human
glucocerebrosidase
gene
CHO Host Cell
Protein
INTERNAL USE ONLY

Cerezyme: Entry into Lysosomes of
Macrophages via Mannose Receptors
Cerezyme
mannose
mannose
normal lysosome receptor
substrate-engorged
lysosome
glucosylceramide
Gaucher cell
INTERNAL USE ONLY
Cerezyme (imiglucerase for infusion)
Dosage & Administration
• Indication: Long-term ERT in confirmed diagnosis Type 1 or Type 3

GD with clinically significant non-neurological manifestations of the
disease.
• IV infusion @ 1u/kg/min @ 60 U/kg body weight once every 14 days
• Improvement in haematological and visceral parameters within 6

months of therapy
− continued use has either stopped progression of or improved bone
disease.
INTERNAL USE ONLY
Key Gaucher Disease Therapeutic Goals
After 12-24 Months Cerezyme Treatment
Skeletal
No bone crisis
No to very mild bone pain
Hematologic
Hemoglobin QoL:
≥11g/dL (females & children)
≥12 g/dL (males) Improve validated
QoL scores
Platelets
within 2-3 years
>120,000/mm3
Visceral
Spleen volume ≤ 8 MN
Liver volume ≤ 1.5 MN
INTERNAL USE ONLY
Pastores et al., Semin Hematol 2004; 41(suppl 5): 4-14, Weinreb et al 2009
Reduction in Liver and Spleen Volumes with
Cerezyme
INTERNAL USE ONLY
Weinreb NJ et al., Am J Med 2002;113:112. Clinical Data
Assessing Bone Disease in Gaucher
• History: growing pattern, bone pain, bone crisis, family connection

• Physical examination: height & growth, stature, deformities,
mobility, pain
• X-ray: clinically affected areas, baseline
• MRI: bone marrow infiltration/local abnormalities investigation –
lumbar spine & femur
Hemorrhagic
• DEXA: bone mineral density – lumbar vertebrae Infarction
Necrosis
Cortical Sclerosis
Osteosclerosis
Erlenmeyer flask
deformity
Loss of
INTERNAL USE ONLY
Cortical Bone
MRI: Bone marrow infiltration with Gaucher cells
Normal Homogeneous infiltration Heterogeneous infiltration

(30 % triglycerides Reduced fat content
70% water) makes Gaucher infiltrated
areas appear darker on T1
INTERNAL USE ONLY
Cerezyme in Gaucher Bone Disease-

Evidence of Efficacy: Bone Biopsy
Pre Cerezyme: Post Cerezyme:
Marrow packed with Decrease in BMB of
Gaucher cells Gaucher cells
INTERNAL USE ONLY

..knees in same patient : Post Cerezyme
60 U
1997 2000
INTERNAL USE ONLY
Courtesy Dr L W Poll, Duisburg
MUCOPOLYSACCHARIDOSIS
INTERNAL USE ONLY
Mucopolysaccharidosis
Mucopolysaccharidosis I
(Also known as Hurler, Hurler-Scheie, and Scheie)
INTERNAL USE ONLY
Mucopolysaccharidosis I (MPS I):
• Deficiency of lysosomal enzyme

-L-iduronidase
• Progressive accumulation of
glycosaminoglycan (GAG)
• Multisystemic, heterogeneous
• Severe morbidity and early
mortality
• Rare (est. incidence 1:100,000)
Age 5
INTERNAL USE ONLY
MPS I Spectrum of Disease
SEVERE ATTENUATED
HURLER HURLER-SCHEIE SCHEIE
Age at diagnosis 0.2–7 years 0.2–36 years 2–54 years
Effect on cognition Pronounced mental delay No/mild mental delay; No

with loss of acquired skills learning disabilities impairment
Mean life expectancy 7 years Approximately Adulthood

(untreated)
20 years
Phenotype distribution* ~65% ~25% ~10%
INTERNAL USE ONLY

*Estimates based on Moore et al. Orphanet J Rare Dis 2008;3:24 and MPS I Registry data
MPS I Signs & Symptoms
Carpal tunnel syndrome2
Skeletal deformities
(Gibbus)1 Hepatosplenomegaly2
Short stature2
Umbilical/inguinal hernia3 Corneal clouding3
1. Courtesy of Emil Kakkis, MD.
2. Courtesy of MPS Society.
INTERNAL USE ONLY 3. Nyhan & Ozand, 1998. Photo reproduced by permission of
Hodder/Arnold Publishers.
Characteristic Facial Dysmorphisms in Severe
MPS I
Changes in appearance (facial coarsening) are progressive, and in severe
MPS I are often what initially prompts parents to seek medical help
 Thick, bushy, and “thatch like” hair
 Prominent forehead, low eyebrows
 Widely spaced eyes (hypertelorism)
 Short flat “saddle” nose with wide, anteverted nostrils
 Hypertrophic gums, small, gapped, poorly implanted teeth
with multiple caries
Courtesy of E. Kakkis, MD
 Enlarged tongue (macroglossia)
 Protruding jaw (prognathism)
 Short neck
 Excess body hair and rough skin texture
Not all patients have all these characteristics !
Patients with attenuated MPS I often have normal appearance
Courtesy of Dr. N. Guffon
INTERNAL USE ONLY

Ocular and Auditory Manifestations of MPS I
 Corneal clouding
• Unilateral or bilateral
• One of the earliest signs of MPS I
 Decreased visual acuity

Courtesy of Dr. J.E. Wraith
 Hearing loss (conductive and neurosensory) due to frequent ear

infections, defective ossification in the middle ear, scarring of the
tympanic membrane, or nerve damage
Hearing loss as well as poor vision can
contribute to developmental delays
INTERNAL USE ONLY

INTERNAL USE ONLY
Confirming the diagnosis of MPS I with
enzyme assay
• Enzyme analysis (“gold standard”)

− IUDA activity can be measured in leukocytes,
plasma, serum, or dried blood spots
Dried blood spot testing
− Enzyme level cannot be used to approximate
phenotype; all patients with MPS I have virtually
undetectable IUDA activity levels
− Newborn screening offers potentials for the future
 Phenotype is largely determined by genotype
INTERNAL USE ONLY
MPS I: ERT
Aldurazyme® (laronidase)
• Indication:
− For patients with Hurler and Hurler-Scheie forms of MPS I and for
patients with the Scheie form who have moderate to severe
symptoms
• Dose:
− 0.58mg/kg once weekly as IV infusion
Aldurazyme is a registered trademark of BioMarin/Genzyme LLC.
For more information please see complete prescribing information at www.aldurazyme.com.
INTERNAL USE ONLY

Shoulder Flexion
(Phase 1/2 extension)
Baseline 6 months 6 years
Duration of Aldurazyme® treatment
INTERNAL USE ONLY
Sifuentes et al. 2007.
FABRY DISEASE
INTERNAL USE ONLY
Fabry-Pathophysiology
Globotriaosylceramide (GL-3)
galactose galactose glucose ceramide
-galactosidase
galactose glucose ceramide
Lactosylceramide
INTERNAL USE ONLY 1Desnick et al 2001, Metabol Mol Bases Inherit Disease:3733-74
2Brady et al 1967, NEJM;276:1163-7
Pathophysiology
Clinical Features of Fabry Disease
Cardiomyopathy
Angiokeratomas
“Whorlelike” or “spokelike”
corneal opacities INTERNAL USE ONLY
End stage kidney disease
Multi-organ Involvement in Fabry
Affected children
Cornea verticillata Fatigue Psychological issues
Hypohidrosis Growth retardation

 dry skin
 heat, cold, and Hearing loss, tinnitus
exercise intolerance
Cardiac Renal
 arrhythmias  hyperfiltration
 conduction abnormalities  microalbuminuria
 valvular dysfunction  GL-3 excretion
 left ventricular hypertrophy
GI dysmotility
 abdominal cramping Angiokeratoma
 diarrhea
 bloating
 nausea
Peripheral neuropathy
 chronic burning pain
 severe episodic pain crises Clinical Manifestations
INTERNAL USE ONLY Eng et al 2006, Genet Med;8:539-48
Progression of Fabry Disease
Adult Male /Female Patients
Fatigue Psychological issues (e.g. depression)
Cornea verticillata
Early stroke, TIAs
Hypohidrosis
 dry skin Hearing loss, tinnitus
 heat, cold, and
exercise intolerance Renal complications
Cardiac complications  decline in GFR
 arrhythmias  (overt) proteinuria
 conduction abnormalities  end-stage renal disease
 valvular dysfunction GI dysmotility
 LVH  abdominal cramping
 myocardial infarction  diarrhea
 heart failure  bloating
 sudden death  nausea
Peripheral neuropathy
 chronic burning pain
Angiokeratoma
 severe episodic pain crises
 paraesthesia
 sensory abnormalities
INTERNAL USE ONLY
Clinical Manifestations
Common Misdiagnoses
• Rheumatoid or juvenile arthritis  Raynaud’s syndrome

 Carditis
• Rheumatic fever
 Auto immune disease
• Fibromyalgia / chronic fatigue
 Connective tissue disorder
syndrome
 Petechiae
• Multiple sclerosis  Vasculitis
• Chronic intermittent  Growing pains
demyelinating polyneuropathy  Etc, etc.
• Neurosis / malingering
INTERNAL USE ONLY
Early Signs and Symptoms
Peripheral Neuropathic Pain
“Fabry small fiber neuropathy”:
There are 2 prominent types of neuropathic pain1,2:
 Chronic burning, nagging pain in the palms of the hands and soles of the feet
 Recurrent attacks of severe pain (“pain crises”)

- often beginning in hands/feet and radiating proximally
- may occur daily
- triggered by, for example, a rapidly changing core body temperature (e.g.
fever, stress, physical activity)
- may be accompanied by unexplained fever
1Schiffmann et al 2002, Acta Paediatr Suppl;91:48-52
2Torvin Moller et al 2007, Nat Clin Pract Neurol;3:95-106
INTERNAL USE ONLY

Cardiac Complications
• Conduction abnormalities and potentially lethal arrhythmias
 Short PR interval at an early stage
 AV block at later stage
 Rhythm disturbance
 Sudden death
• Left ventricular hypertrophy (LVH)

 Diastolic dysfunction
 Can progress to heart failure
• Impaired exercise capacity

• Angina pectoris, myocardial infarction
• GZIN.CERZ.16.05.0012
Others: valvular disease, lymphedema,
LVH on MRI
thrombosis
1Schiffmann et al 2009, NDT; 24:2102-11

INTERNAL USE ONLY Kampmann et al 2002, Z Kardiol;91:786-95
Linhart et al 2002, Acta Paediatr Suppl;91:15-20
Decline in GFR
● Natural decline in eGFR in Fabry patients1, *
Baseline eGFR in ml/min/1.73 m2

≥60 <60
Males Females Males Females
Yearly eGFR decline −3.0 −0.9 −6.8 −2.1
*Annual GFR decline in normal adult population is -1 ml/min/1.73 m2 (ref. 3)
 End-stage renal disease in the 3rd to 5th decades of life
1Schiffmannet al 2009, Nephrol Dial Transplant; 24:2102-11
INTERNAL USE ONLY
2Ortizet al. Nephrol Dial Transplant 2008, 23: 1600-7
3Lindeman et al 1985. J Amer Ger Soc 33:278-85
Fabry Disease: ERT
• Fabrazyme®(agalsidase beta)
• Indication: Use in patients with Fabry
Disease
INTERNAL USE ONLY
POMPE DISEASE
INTERNAL USE ONLY
Pompe Disease
INTERNAL USE ONLY
Pompe affects skeletal and smooth muscles
• JC Pompe discovered the disease in

1932.
• The affected gene was identified in
1965 by Henri G. Hers and he
characterized the disease as resulting
from the buildup of glycogen in cells.
• Deficiency of the enzyme alpha
glucosidase is the cause.
JC POMPE
INTERNAL USE ONLY
Symptoms
• Early onset
• Floppy baby
• Cardiac and respiratory infections/failure
• Other difficulties: Inability to gain weight
• Death (within 1 year)
• Late onset
• Skeletal and joint muscles weakness (LGMW)
• Difficulty breathing
• Therapy
• Myozyme infusion 20mg/kg
INTERNAL USE ONLY

Multidisciplinary therapy approach is
needed
INTERNAL USE ONLY
Signs & Symptoms: Summary
INTERNAL USE ONLY
Signs & Symptoms: Summary
INTERNAL USE ONLY
Diagnosis is simple: Dried Blood Spot
(DBS) testing to create timely diagnosis
• Offer reagents free of charge to any diagnostic lab
through CDC
• Offer knowledge transfer and Lab upgrade for LSD

screening
• Provision for DBS (Dried Blood Spot) testing in tandem

with leading medical institutions
− # First collaboration with Department of Medical Genetics, SGRH (Sir

Ganga Ram Hospital, Delhi)
− # Convenient and accurate sample collection and transfer technique
INTERNAL USE ONLY
Lab Diagnosis :Simple Blood Test
• Measurement of enzyme activity

Glucocerebrosidase (acid β glucosidase) assay
− Can be done on leukocytes (peripheral blood) or cultured fibroblasts (skin biopsy)
− Enzyme activity levels
− Adults: usually 10% to 30% of normal
− Children (severe cases): < 10% of normal
− Residual activity does not predict clinical outcome
• Genotyping
− DNA analysis
− Reliable way to test carriers among relatives at risk
− Genotype does not predict clinical phenotype
INTERNAL USE ONLY

Summary of Treatments available:
Pioneering ERTs
Aldurazyme ® Fabrazyme® Cerezyme ® Myozyme ®
(laronidase) (agalsidase- (imiglucerase) (alglucosidase
Indication: alpha)
• Indication: beta)
Indication: • Use in Type I Indication:
− Hurler and Hurler-
Scheie forms of • Use in patients and Type 3 • Use in Pompe
MPS I with Fabry Gaucher disease
Disease disease
− Scheie form who
have moderate to
severe symptoms
INTERNAL USE ONLY
Aldurazyme is a registered trademark of BioMarin/Genzyme LLC.
For more information please see complete prescribing information at www.aldurazyme.com.
Our strength: our patients
INTERNAL USE ONLY
Thank you!
INTERNAL USE ONLY

Lysosomal Storage Disorders

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Hope | Believe | Achieve

Govind | Pompe disease | India

Lysosomal Storage Disorders

1983 1991 2001 2011

15 Years Journey of Gaucher Patient

Our Strength: Our Patients

What are Lysosomal Storage Disorders (LSDs)?

Specific Gene mutation → specific enzyme deficiency → defective

INTERNAL USE ONLY

LSDs Result Due to Enzyme Deficiency

• Caused by Inherited enzyme deficiencies that result in

• Severity generally varies with the degree of protein deficiency.

Gaucher cell 1882

Phillip Ernest GAUCHER

LSDs are extremely ‘Rare’

• Overall, LSDs affect 1 in about every 7,700 babies born.

• Individually, however, each of the diseases is considerably rarer,

• Because of these diseases’ relative rarity, it can be difficult to find

LSDs (based on neonatal screening)

INTERNAL USE ONLY

LSDs are progressive diseases

There is a Need for Timely Diagnosis

• Progressive, life-threatening , multisystemic diseases

• Treatment is available for several LSDs

Some Treatable LSDs

Gaucher Disease - Cerezyme

LSD : Red Flags in clinical practice

• Unusual facial features (sometimes with enlarged

INTERNAL USE ONLY

Pathogenesis of Gaucher Disease

INTERNAL USE ONLY

Gaucher Disease Phenotypes

1/50,000 (pan-ethnic) 1/100,000 1/100,000

Lifespan 6 to > 80 y ~2y 2 to 60 y

Visceromegaly mild to severe moderate to severe mild to severe

INTERNAL USE ONLY

Gaucher Disease: Clinical Presentation

INTERNAL USE ONLY

Gaucher disease: Presentation in Children

Children or adolescents with GD Type 1 often have marked splenomegaly, easy

INTERNAL USE ONLY

Multisystem Involvement / Bone

INTERNAL USE ONLY

• Diagnosis is often delayed, especially in GD type 1

• Presumptive diagnosis can be based on

Diagnosing GD: Why is GD missed?

GD 1 CML ALL NHL MM ITP

Typical age at 2-3 (children)

INTERNAL USE ONLY  Yes Sometimes

Treatment Options for Gaucher

(e.g., supportive care for pain, (enzyme replacement with

Optimal care involves both supportive and disease-specific treatment and

INTERNAL USE ONLY

CHO Host Cell

INTERNAL USE ONLY

• Indication: Long-term ERT in confirmed diagnosis Type 1 or Type 3

• IV infusion @ 1u/kg/min @ 60 U/kg body weight once every 14 days

• Improvement in haematological and visceral parameters within 6

Assessing Bone Disease in Gaucher

• History: growing pattern, bone pain, bone crisis, family connection

MRI: Bone marrow infiltration with Gaucher cells

Normal Homogeneous infiltration Heterogeneous infiltration

Cerezyme in Gaucher Bone Disease-

Pre Cerezyme: Post Cerezyme: