Galactose-1-phosphate Uridylyltransferase Deficiency - Genetics

Genetics

All forms of galactosemia are inherited in an autosomal recessive manner, meaning individuals affected with classic galactosemia must have inherited a mutated copy of the GALT gene from both parents. Each child from two carrier parents would have a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting normal versions of the gene from each parent.

There are several variants in the GALT gene, which have different levels of residual enzyme activity. A patient homozygous for the one of the severe mutations in the GALT gene (commonly referred to as G/G) will typically have less than 5% of the enzyme activity expected in an unaffected patient. Duarte galactosemia is caused by mutations that produce an unstable form of the GALT enzyme, with reduced promoter expression. Patients who are homozygous for Duarte mutations (D/D) will have reduced levels of enzyme activity compared to normal controls, but can often maintain a normal diet. Compound heterozygotes (D/G) will often be detected by newborn screening, and treatment is based on the extent of residual enzyme activity.