PEDBASE.org - The Pediatric Database - Detailed information of GALACTOSEMIA-3

GALACTOSEMIA-III

DEFINITION:

A disorder of galactose metabolism characterized by a deficiency of uridyl diphosphogalactose-4-epimerase activity resulting in benign and severe forms of disease.

EPIDEMIOLOGY:

incidence: very rare
age of onset:
- newborn thru infancy (severe form)
risk factors:
- familial - autosomal recessive
  - chrom.#: ?
  - gene: uridyl diphosphogalactose-4-epimerase
- M = F

PATHOGENESIS:

1. Background

uridyl diphosphogalactose-4-epimerase assists in the conversion of galactose-1-phosphate to glucose-1-phosphate by catalyzing the conversion of UDP-glucose to UDP-galactose

2. Genetic Defect

genetic defect -> deficiency of uridyl diphosphogalactose-4-epimerase activity -> accumulation of galactose
two forms of the disease based upon the tissue distribution of the enzyme defect:

1. Benign Form

patients completely asymptomatic
enzyme deficiency in blood cells only (leukocytes, lymphocytes, erythrocytes) but not in other tissues where activity is normal

2. Severe Form

patients clinically identical to the classical form of galactosemia (see Galactosemia-I)
enzyme deficiency is in blood cells and fibroblasts (where it is <10% of normal)

CLINICAL FEATURES:

1. Benign Form

completely asymptomatic
discovery of this form usually an incidental finding during a newborn screening exam when the concentration of galactose-1-P is found to be elevated in RBC's

2. Severe Form (see Galactosemia-I)

1. Hepatic and Gastrointestinal Manifestations

lethargy, irritability, vomiting, seizures
feeding difficulties, poor weight gain, failure to thrive (FTT)
jaundice, hepatomegaly, hypoglycemia
ascites, splenomegaly
hepatic cirrhosis +/- complications

2. Fanconi Syndrome

episodes of vomiting, dehydration, weakness, & unexplained fever
anorexia, constipation
polydipsia and polyuria
FTT and growth failure
rickets

3. Other Manifestations

1. Neurological

mental retardation, seizures, pseudotumor cerebri

2. Endocrine

primary or secondary amenorrhea
? increased risk of ovarian cancer

3. Ocular

cataracts

INVESTIGATIONS (Severe Form):

1. Urine

test for reducing substance after feeding human or cow's milk or formula containing lactose
positive for reducing substance (galactosuria)
- positive Clinitest but negative Clinistix indicates that the reducing substance is not glucose
galactose identified by chromatography

2. Serum

elevated transaminases and conjugated hyperbilirubinemia
elevated FSH and LH with decreased estrogen

3. Liver Biopsy

fatty infiltration
pseudoacini
macronodular cirrhosis

4. Diagnosis

deficiency of uridyl-diphosphogalactose-4-epimerase activity in
RBC's and fibroblasts

5. Fanconi Syndrome

specific urine and serum findings
see "Fanconi Syndrome - Renal"

MANAGEMENT:

1. Diet

eliminate lactose and galactose from the diet
with early and good dietary control good prognosis

2. Fanconi Syndrome

manage underlying disorder

Pediatric Database - GALACTOSEMIA-3

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