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Galactosemia

OMIM ID:

autosomal recessive

Galactosemia

Alternate Names

classic galactosemia
galactosemia I
GALT deficiency

Defective Genes

GALT

Clinical Characteristics

Ocular Features

Neonatal cataracts are found among at least 30% of infants with this disorder.  However, early (before 17 days of age) dietary restrictions can prevent their formation or even lead to regression.  They result from the osmotic imbalance caused by the presence of accumulated galactitol.  Neonates may suffer vitreous hemorrhages from the coagulopathy but this is rare.

Systemic Features

In spite of early and adequate treatment, however, many adults have residual problems.  Cataracts have been found in 21%, decreased bone density in 24%, tremor in 46%, ataxia in 15%, and dysarthria in 24%.  Few patients of either sex have children and all females have premature ovarian insufficiency.  Depression and anxiety are present in 39-67%.  It has been estimated that there is a twofold increase in the odds of depression with each 10 year increment of age.

Genetics

Inheritance

This is an autosomal recessive disorder resulting from mutations in the GALT gene (9p13) encoding galactose-1-phosphate uridylyltransferase.

For other disorders of galactose metabolism see galactose epimerase deficiency (230350) and galactokinase deficiency (230200).

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

Treatment with a lactose- and galactose-free diet within the first 3-17 days can prevent the formation of cataracts.  Few need surgical removal.  Liver function improves and a reduction in icterus can be seen.  It can also prevent fatal E. coli sepsis.  However, long term effects have been disappointing as many patients still develop mental and motor dysfunction as well as speech difficulties (dyspraxia).  The long term outcome seems to depend upon the level of GALT enzyme activity which varies considerably.

Special education and speech therapy may be beneficial.  Depression in older patients should be offered where indicated.

Selected Resources

Publications

Displaying 1 - 4 of 4

Long-term outcome in 134 patients with galactosaemia

PubMedID: 8444204

The adult galactosemic phenotype

PubMedID: 21779791

The molecular biology of galactosemia

PubMedID: 11261429

Vitreous hemorrhage as an ophthalmic complication of galactosemia

PubMedID: 8969739