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Galactose Epimerase Deficiency

OMIM ID:

autosomal recessive

Galactose Epimerase Deficiency

Alternate Names

GALE deficiency
galactosemia III

Defective Genes

GALE

Clinical Characteristics

Ocular Features

At least some patients have childhood cataracts which may be unilateral.  Direct assay of GALE activity in lenses shows a significant decrease in at least some patients.

Systemic Features

This rare disorder of galactose metabolism has an especially wide range of expression.  Some patients seem to have little or no clinical disease whereas others are severely affected.   Early cases were found to have epimerase deficiency only in circulating red blood cells while other cells seemed to have normal levels of the enzyme.  Some of these patients have virtually no symptoms.  Later, cases were found that resembled classic galactosemia (230400) in presentation and even responded to galactose restriction diets. Current thought favors the hypothesis that the same gene defect is responsible for the entire continuum of clinical disease.  Red blood cells have elevated levels of galactose-1-phosphate.

 

Genetics

Inheritance

This is an autosomal recessive disorder resulting from mutations in the GALE gene (1p36-p35.

Another disorder of galactose metabolism causing early onset cataracts is galactokinase deficiency (230200) caused by mutations in GALK1.

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

A galactose-restricted diet is beneficial.  Since these patients are unable to utilize the endogenous pathway of synthesis for UDP-galactose they are dependent on exogenous galactose and therefore some galactose is required in the diet.

Selected Resources

Publications

Displaying 1 - 3 of 3

Frühkindliche Katarakt bei familiärem UDP-Galaktose-4-Epimerase-Mangel - eine Kasuistik12

PubMedID: 11258124

UDPgalactose epimerase in lens and fibroblasts: Activity expression in patients with cataracts and mental retardation

PubMedID: 10896300

UDPgalactose epimerase in lens and fibroblasts: Activity expression in patients with cataracts and mental retardation

PubMedID: 10896300