Galactosaemia

Galactosaemia caused by galactose-1-phosphate uridyl transferase deficiency has a birth incidence of 1:40,000. The disorder is caused by the accumulation in the blood of one of the sugars (galactose) in milk. Prompt treatment with a special formula that does not contain galactose will completely prevent serious illness. Untreated babies with galactosaemia may become very sick and die.

Clinical features:

The severe form of this disease is due to almost total deficiency of galactose-1-phosphate uridyl transferase (Gal-1-PUT) enzyme activity in all cells of the body. The early clinical features include neonatal hypoglycaemia, vomiting, jaundice, and liver failure. Death may result from liver failure or gram-negative sepsis within one to two weeks of birth. If the infant survives the neonatal period, failure to thrive, cirrhosis, kidney disease (proximal renal tubular acidosis), cataracts and mental retardation may develop.

Mild variants:

There are several genetic variants with only partial enzyme deficiency. One very common one is the Duarte variant. Babies with variant galactosaemia are asymptomatic and do not need treatment. They may be detected because of a mild elevation of galactose metabolites due to reduced activity in the Gal-1-PUT enzyme assay in the first three months of life.

Galactokinase deficiency:

This rare defect is associated only with the development of cataracts in infancy and possibly with some degree of mental retardation. The life-threatening symptoms of severe galactosaemia do not occur.

Laboratory tests:

Elevations of galactose metabolites are detected using a manual fluorometric assay for galactose and/or galactose-1-phosphate. Blood galactose metabolites are quite frequently elevated (1 mmol/L) in normal neonates. They are greatly elevated in infants with galactose-1-phosphate uridyl transferase (Gal-1-PUT) and galactokinase deficiency, but only when they are receiving lactose-containing feeds. When galactose metabolites are elevated, a follow up test is thin layer chromatographic separation of the sugars. This allows the determination of levels of galactose or galactose-1-phosphate. The metabolite increase gives an indication of the enzyme defect leading to galactosaemia. Samples with elevated galactose metabolites are tested urgently for Gal-1-PUT activity.

Treatment:

The galactosaemia syndromes are effectively treated by a rigid dietary exclusion of all galactose.

Screening considerations:

The Gal-1-PUT assay should be abnormal in all severe (classical) galactosemic infants even if the specimen is obtained before lactose is ingested, unless the infant has had an exchange transfusion. Obtain a specimen before an exchange transfusion. Galactose accumulation depends on lactose ingestion so that blood galactose is normal in infants receiving soy-based formula or other forms of nutrition. Galactosaemia may be rapidly fatal and should be considered in any infant with non-glucose reducing substances in the urine, although this is not a reliable test for galactosaemia.