Disorders of Galactose Metabolism

Summary

Three inborn errors of galactose metabolism are known, one for each step in the Leloir pathway of galactose conversion to glucose. The first, galactokinase deficiency, is discovered either through newborn screening for hypergalactosemia, or by the chance finding of reducing substance in urine, or by selective urine screening for galactose in infants or older persons examined for nuclear cataracts. In the undiagnosed newborn drinking milk, cataracts develop insidiously within a few weeks as the only clinical manifestation. Galactose-galactitol-glucose diabetes is the only chemical sign. Diagnosis is made by enzyme assay on blood cells or fibroblasts. For treatment, milk and milk products are eliminated from the diet. In transferase deficiency or galactosemia, the second step in the Leloir pathway is blocked. In most developed countries, this defect is discovered through newborn screening, and the more serious clinical symptoms are avoided by prompt treatment. Infants who remain undiagnosed develop symptoms and signs of liver and kidney failure and succumb to sepsis. Survivors develop cataracts and mental impairment. Diagnosis is suggested by the presence of reducing substance in the urine of the fed newborn, and it is made by enzyme assay on blood cells, a liver biopsy specimen, or fibroblasts. Lifelong exclusion of all galactose from the diet is stipulated, but difficult to achieve. Partial transferase deficiency is more frequent than the complete defect. It is treated by a less-than-complete removal of dietary galactose, usually restricted to the first few months of life. The third defect of the Leloir pathway, epimerase deficiency, occurs in both a benign mild form and a severe and crippling form. Both are discovered through newborn screening, using methods sensitive to galactose-1-phosphate and are diagnosed by enzyme assay on blood cells or fibroblasts. Infants with the mild form do not seem to require treatment. The two documented severe cases showed clinical features reminiscent of untreated galactosemia; their dietary treatment proved difficult and unsatisfactory.

“Whenever you consider a galactose disorder, stop milk feeding first and only then seek a diagnosis.”