CLINICAL, BIOCHEMICAL AND MOLECULAR FINDINGS IN A 2-GENERATION MORQUIO-A FAMILY

Mucopolysaccharidosis type IVA (Morquio A) is caused by a deficiency o f N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme capable of clea ving the sulfate group from both N-acetylgalactosamine-6-sulfate and g alactose-6-sulfate. We describe here a two-generation Morquio A family with two distinct clinical phenotypes. The two probands from the seco nd generation showed intermediate signs of the disease whereas their a ffected mother, aunt and two uncles had only very mild symptoms, Galac tose-6-sulfatase (GALS) activity in leukocytes and fibroblasts of the affected family members was clearly deficient, Molecular genetic analy sis of the GALNS gene revealed that two different point mutations segr egate in the family, which correlated well with the clinical phenotype . The probands with intermediate symptoms were compound heterozygotes for the mutations R259Q and R94G the latter one being inherited from t he unaffected father. The mother and her affected siblings with the un usually mild phenotype were proven to be homozygous for the novel miss ense point mutation R259Q.