Galactose metabolism disorder (galactosemia) in children

Galactosemia is an inherited disorder caused by defects in galactose metabolism. Symptoms of galactosemia include liver and kidney dysfunction, cognitive decline, cataracts, and premature ovarian failure. Diagnosis is based on red blood cell enzyme testing. Treatment consists of a galactose-free diet. The prognosis for physical development is usually good with treatment, but verbal and nonverbal intelligence tests are often impaired.

ICD-10 code

E74.2 Disorders of galactose metabolism.

Epidemiology of galactosemia

Galactosemia type I is a pan-ethnic disease with an average incidence of 1 in 40,000 live births in European countries.

Galactosemia, type II - in European countries the incidence rate is 1 in 150,000 live births. Higher incidence is noted in Romania and Bulgaria. It is found with high frequency in Roma - 1 in 2500.

Galactosemia type III is a rare inherited metabolic disorder. The benign form is common in Japan (1 in 23,000 births).

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What causes galactosemia?

Galactosemia is caused by an inherited deficiency of one of the enzymes that converts galactose into glucose.

Causes and pathogenesis of galactosemia

Symptoms of Galactosemia

Galactose is present in dairy products, fruits and vegetables; 3 clinical syndromes are caused by autosomal recessive inherited deficiencies of various enzymes.

Galactose-1-phosphate uridyltransferase deficiency

Deficiency of this enzyme results in classic galactosemia. The incidence is 1/62,000 births; the carrier frequency is 1/125. Infants develop anorexia and jaundice within days to weeks of consuming breast milk or lactose-containing formula. Vomiting, hepatomegaly, poor growth, lethargy, diarrhea, and septicemia (usually due to Escherichia coli) and renal abnormalities (eg, proteinuria, aminoaciduria, Fanconi syndrome) develop, leading to metabolic acidosis and edema. Hemolytic anemia may also develop. If untreated, children remain short in stature and develop cognitive, speech, gait, and balance impairment during adolescence; many also develop cataracts, osteomalacia (due to hypercalciuria), and premature ovarian failure. Patients with the Duarte variant have much milder clinical manifestations.

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Galactokinase deficiency

Patients develop cataracts due to the production of galactitol, which osmotically damages the lens fibers; idiopathic intracranial hypertension (pseudotumor cerebri) is rare. The incidence is 1/40,000 births.

Uridyl diphosphate galactose-4-epimerase deficiency

Benign and severe forms of the disease may occur. The incidence of the benign form is 1/23,000 births in Japan; for the more severe forms, the incidence is unknown. The benign form is limited to red blood cells and white blood cells and causes no clinical manifestations. The severe form causes a syndrome indistinguishable from classic galactosemia, although hearing loss is sometimes also noted.

Symptoms of Galactosemia

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Classification of galactosemia

To date, three hereditary diseases are known that are caused by a deficiency of enzymes involved in galactose metabolism: galactosemia type I (galactose-1-phosphate uridyltransferase deficiency, classical galactosemia), galactosemia type II (galactokinase deficiency) and galactosemia type III (galactose-4-epimerase deficiency).

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Diagnosis of galactosemia

The diagnosis is suspected clinically, with evidence in favor of it from elevated galactose levels and the presence of reducing substances other than glucose (eg, galactose, galactose-1-phosphate) in the urine; the diagnosis is confirmed by testing enzymes in red blood cells and liver tissue. Most states require newborn screening for galactose-1-phosphate uridyltransferase deficiency.

Diagnosis of galactosemia

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Screening for galactosemia

Among these diseases, galactosemia type I is the most severe pathology requiring urgent correction. Mass screening of newborns, conducted in many countries, is aimed at identifying this form of galactosemia.

Treatment of galactosemia

Treatment of galactosemia involves eliminating all sources of galactose from the diet, primarily lactose, which is the source of galactose present in all dairy products, including milk-based infant formulas, and the sweeteners used in many foods. A lactose-free diet prevents acute toxicity and reverses some symptoms (eg, cataracts) but may not prevent neurocognitive impairment. Many patients require supplemental calcium and vitamins. Patients with epimerase deficiency must consume small amounts of galactose to provide a supply of uridyl-5'-diphosphate galactose (UDP-galactose) for various metabolic processes.

Treatment of galactosemia