GALACTOSEMIA

DEFINITION
Galactosemia (British Galactosaemia) is a rare genetic metabolic disorder that affects an
individual's ability to metabolize the sugar galactose properly.
Galactosemia follows an autosomal recessive mode of inheritance that confers a
deficiency in an enzyme responsible for adequate galactose degradation.
Friedrich Goppert (18701927), a German Physician, first described the disease in 1917,
with its cause as a defect in galactose metabolism being identified by a group led by
Herman Kalckar in 1956.
Galactosemia
Epidemiology
Classic galactosemia occurs in approximately 1 of 60,000 live births .
However, the reported incidence of galactosemia varies geographically from 1 in 30,000
to 40,000 in Europe to one in one million in Japan.
The estimated incidence in the United States is 1 in 53,000 live births.
Galactosemia is ten times more common within the Irish Traveller population.

Race
It occurs in all races, but the variants are dependent on the exact gene defect.

Epidemiology
Mortality/Morbidity
Aside from the high mortality rate in newborn infants with sepsis caused by Escherichia
coli, life expectancy has never been studied in patients with galactosemia.
Most patients appear to reach adulthood following institution of a galactose-restricted
diet.
Sex
Galactosemia equally affects males and females.

Age
Galactosemia is most often diagnosed in infancy by newborn screening because all
states include galactosemia as part of their newborn screen.
Variant forms of galactosemia can present later.
Pathophysiology
Normally, galactose is metabolized in the body to glucose,
each step in the metabolic pathway being carried out by a
specific organic catalyst, or enzyme.

In galactosemia, the enzyme that catalyzes the second step,
Galactose-1-Phosphate Uridyl Transferase(GALT) converting
galactose-1-phosphate to glucose-1-phosphate, is not active.

As a result of this metabolic block, there is an accumulation of
galactose-1-phosphate in body tissues.
Galactosemia
Variants of the disease
The disease can be variable in terms of severity with a Duarte variant that is comparatively
benign.
There are many variants of the disease but most affect one of three enzymes.

GALT deficiency is the most common abnormality. The enzyme converts galactose-1-
phosphate and UDP glucose to UDP galactose and glucose-1-phosphate. Patients with
GALT deficiency have abnormal galactose tolerance.
Galactokinase converts galactose to galactose-1-phosphate and deficiency is rather
uncommon.
Uridine diphosphate (UDP) galactose-4-epimerase epimerises UDP galactose to UDP
glucose and deficiency is also less common.
Clinical signs and symptoms
Infants with galactosemia can develop symptoms in the first few days of life if they eat
formula or breast milk that contains lactose.
The symptoms may be due to a serious blood infection with the bacteria E. coli.
An infant with classic galactosemia usually appears normal at birth.
Early symptoms
Early symptoms may include:
Yellowing of the skin and whites of the eyes (jaundice)
Vomiting
Poor weight gain(baby refuses to eat formula containing food)
Feeding difficulties
Irritability
Convulsions
Lethargy
Late symptoms
If left untreated, later symptoms and complications may include:
Opaque lenses of the eyes known as cataracts
Enlarged liver, enlarged spleen
Intellectual disability
Sepsis caused by a specific bacteria
Scarring of the liver known as cirrhosis
Liver failure
Kidney problems
Swelling of the extremities or abdomen
If untreated..
If dietary restrictions are started right away, it may be possible to prevent acute toxicity.
However, long-term complications may still occur. These may include:
Poor growth
Learning disabilities
Speech and language problems
Fine and gross motor skill delays
Ovarian failure
Cataractsusually regress with dietary treatment, leaving no remaining visual impairment
Decreased bone mineral density
Signs and symptoms
Mutations
Mutations in the GALE, GALK1, and GALT genes cause galactosemia.
The GALE, GALK1, and GALT genes provide instructions for making enzymes that are
essential for processing galactose obtained from the diet.
These enzymes break down galactose into another simple sugar, glucose, and other
molecules that the body can store or use for energy.
Type I or classic galactosemia
Mutations in the GALT gene are responsible for classic galactosemia (type I).
Most of these genetic changes almost completely eliminate the activity of the enzyme
produced from the GALT gene, preventing the normal processing of galactose and
resulting in the life-threatening signs and symptoms of this disorder.
Another GALT gene mutation, known as the Duarte variant, reduces but does not
eliminate the activity of the enzyme. People with the Duarte variant tend to have much
milder features of galactosemia.
Type II and Type III
Galactosemia type II results from mutations in the GALK1 gene, while mutations in the
GALE gene underlie Galactosemia type III.
Like the enzyme produced from the GALT gene, the enzymes made from the GALK1 and
GALE genes play important roles in processing galactose.
A shortage of any of these critical enzymes allows galactose and related compounds to
build up to toxic levels in the body.
The accumulation of these substances damages tissues and organs, leading to the
characteristic features of galactosemia.
Mutations
Type OMIM Gene Locus Enzyme Name
Type I 230400 GALT 9p13 Gal1P Uridyl Transferase Classic Galactosemia
Type II 230200 GALK1 17q24 Galactokinase Galactokinase deficiency
Type III 230350 GALE 1p36-p35 UDP gal Epimerase Galactose Epimerase deficiency
Treatment
Galactosemia is an inherited genetic disorder of metabolism.
This cannot be cured.
The disease can only be managed to prevent complications of the condition.

Management
The only way to manage galactosemia is to eliminate lactose and galactose from the diet
completely.
People with this condition must avoid all milk, milk-containing products and other foods
that contain galactose.
Infants having the galactosemia will not allow to take the lactose containing foods.
Breast feeding and cow milk formula must be stopped.


Diet
Avoid all products that contain or produce galactose.
This includes milk or milk by-products, such as
Milk
Casein
Lactose sugar
Powdered/ Condensed Milk
Yoghurt
Also to be avoided
Buttermilk Solids
Sour Cream
Legumes
Soy sauce
Organ Meats (liver, heart, kidney brains, sweetbreads, pancreas)
Hydrolyzed proteins
Fermented soy
Infants can be fed with
Soya formula
Meat-based formula or Nutramigen (a protein hydrolysate formula)
Any lactose-free formula
Calcium supplements are recommended.

Monitoring dietary treatment
When a baby with galactosemia starts drinking a galactose-free formula or when a child
or adult with galactosemia is avoiding galactose in foods, it is helpful to see how their
bodies react to the change in diet. This is called treatment monitoring.
There are a number of methods used to do this:
take blood to measure Gal-1-P in the red blood cells
take blood to measure galactitol in the plasma
take a urine sample to measure galactitol
The most common way to monitor treatment is to measure Gal-1-P in blood. For many
clinics, the treatment goal is to reduce and maintain Gal-1-P levels less than 4.0 mg/dL (or
about 140 g/g hemoglobin)
Journal 1 : The molecular biology of
galactosemia
Published in Journal of Medicine, 1998.
Louis J Elsas; and Kent Lai
Department of Pediatrics, Division of
Medical Genetics, Emory University
School of Medicine, Atlanta, Georgia

Abstract :
Classic galactosemia is an autosomal
recessive disorder caused by the
deficiency of galactose 1-phosphate
uridyltransferase (GALT).
Although the potentially lethal, neonatal
hepatotoxic syndrome is prevented by
new-born screening and galactose
restriction, long-term outcome for older
patients with galactosemia remains
problematic.
Journal 1 cont.
After the cloning and sequencing of the GALT gene, more than 130 mutations in the GALT
gene have been associated with GALT deficiency.
This review relates them to function and clinical outcome. Two common mutations, Q188R
and K285N, account for more than 70% of G alleles in the white population and are
associated with classic galactosemia and impaired GALT function.
Journal 2 : Analysis of galactosemia
Published in Journal of Pediatrics, Vol 33,
Issue 2, 1990.
M.D. Eugene O. Goldstein, M.D. Julius M.
Ennis
Abstract :
A case of galactosemia, in a 2 1/2 month old
infant, has been reported and the literature
reviewed.
Our case had the features common to all the
other casesnamely, failure to gain weight and
develop properly, melituria, and albuminuria.
In addition, our patient showed cataracts, which
have been described in 50 per cent of the other
cases. By the removal of lactose from the diet,
there was subsidence of all the pathologic signs
and symptoms except for the enlarged liver.
Carbohydrate studies were done, showing a
normal glucose tolerance curve, a high
galactose tolerance curve, and antagonistic
effects of glucose and galactose upon one
another.

THANK YOU
Nallathambi, Aiswarya Bharathi
Nallagatla, Susmitha
Narayanaswamy, Nithya
Narra, Vindhya Rani