GALACTOSEMIA

SCIENTIFIC BACKGROUND

Classic galactosemia is a severe autosomal recessive inherited metabolic disease caused by pathogenic variants in the GALT gene. The enzyme galactose-1-phosphate uridyltransferase mediates the degradation of galactose. In case of an enzyme deficiency, the metabolite galactose-1-phosphate accumulates in the liver, brain, kidney and erythrocytes, resulting in severe liver dysfunction. In the later stages of the disease, vomiting, lethargy, icterus and hepatomegaly occur when galactose is ingested in the form of breast milk or infant food. There is also a tendency to sepsis with E. coli. Variants in the GALT gene leading to severe enzyme deficiency with a residual activity of <1% cause the classic form. Variants with higher residual activity show a milder phenotype or even an absence of symptoms.

The diagnosis of galactosemia is part of newborn screening. In case of abnormal findings, the diagnosis can be confirmed by molecular genetics. An early detection allows timely initiation of therapy by galactose restriction diet. The prognosis of the disease depends on factors such as age at diagnosis, severity of the disease and compliance with the diet. However, long-term complications occur even with adequate treatment.

References

Coelho AI et al. 2017, J Inherit Metab Dis 40(3):325 / Berry GT. Classic Galactosemia and Clinical Variant Galactosemia. 2000 Feb 4 [Updated 2017 Mar 9]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.