MOLECULAR CHARACTERIZATION OF A UNIQUE PATIENT WITH EPIMERASE-DEFICIENCY GALACTOSEMIA

Inherited deficiencies of UDP-galactose 4-epimerase (GALE) have been a ssociated with two distinct phenotypes. The vast majority of North Ame rican patients are clinically asymptomatic, are identified through new born screening programmes for classical galactosaemia, and are of Afri can-American descent. At least two symptomatic patients have been repo rted, one Pakistani and the other Asian Muslim, both with severe compl ications in the neonatal period and subsequent mental retardation. Thr ough newborn screening, we have identified a GALE-deficient patient wh o is of mixed Pakistani/caucasian ancestry. He was clinically well in the neonatal period on a lactose-containing diet, and biochemical stud ies, including urine reducing sugars and galactitol, were consistent w ith a diagnosis of peripheral GALE deficiency. Although early developm ental milestones were met normally, he now shows significant developme ntal delays in both motor and language skills. Mutational analysis rev ealed this patient to be a compound heterozygote at the GALE locus, wi th mutations N34S and L183P identified in the patient and confirmed in the parents. This report represents the first characterization of spe cific mutations in a GALE-deficient patient in conjunction with bioche mical and clinical phenotype, and facilitates further studies of the G ALE enzyme and its role in the different clinical forms of epimerase-d eficiency galactosaemia.