Molecular characterization of a unique patient with epimerase‐deficiency galactosaemia

Inherited deficiencies of UDP‐galactose 4‐epimerase (GALE) havebeen associated with two distinct phenotypes. The vast majority of North American patients are clinically asymptomatic, are identified through newborn screening programmes for classical galactosaemia, and are of African‐American descent. At least two symptomatic patients have been reported, one Pakistani and the other Asian Muslim, both with severe complications in the neonatal period and subsequent mental retardation. Through newborn screening, we have identified a GALE‐deficient patient who is of mixed Pakistani/caucasian ancestry. He was clinically well in the neonatal period on a lactose‐containing diet, and biochemical studies, including urine reducing sugars and galactitol, were consistent with a diagnosis of peripheral GALE deficiency. Although early developmental milestones were met normally, he now shows significant developmental delays in both motor and language skills. Mutational analysis revealed this patient to be a compound heterozygote at the GALE locus, with mutations N34S and L183P identified in the patient and confirmed in the parents. This report represents the first characterization of specific mutations ina GALE‐deficient patient in conjunction with biochemical and clinical pheno‐type, and facilitates further studies of the GALE enzyme and its role in the different clinical forms of epimerase‐deficiency galactosaemia.