title: Clinical, biochemical and molecular findings in a two-generation Morquio A family.
abstract: Mucopolysaccharidosis type IVA (Morquio A) is caused by a deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme capable of cleaving the sulfate group from both N-acetylgalactosamine-6-sulfate and galactose-6-sulfate. We describe here a two-generation Morquio A family with two distinct clinical phenotypes. The two probands from the second generation showed intermediate signs of the disease whereas their affected mother, aunt and two uncles had only very mild symptoms. Galactose-6-sulfatase (GALS) activity in leukocytes and fibroblasts of the affected family members was clearly deficient. Molecular genetic analysis of the GALNS gene revealed that two different point mutations segregate 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 the unaffected father. The mother and her affected siblings with the unusually mild phenotype were proven to be homozygous for the novel missense point mutation R259Q.
authors.affiliation: Department of Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Tylki-Szymańska
authors.forename: B
authors.initials: B
authors.lastname: Czartoryska
authors.forename: S
authors.initials: S
authors.lastname: Bunge
authors.forename: O P
authors.initials: OP
authors.lastname: van Diggelen
authors.forename: W J
authors.initials: WJ
authors.lastname: Kleijer
authors.forename: B J
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: J G
authors.initials: JG
authors.lastname: Huijmans
authors.forename: D
authors.initials: D
authors.lastname: Górska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002811:Chondroitinsulfatases / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005192:Family Health; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives / Q000378:metabolism; D005796:Genes / Q000235:genetics; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007632:Keratan Sulfate / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D013429:Sulfatases / Q000097:blood / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; C086947:galactose 6-sulfate; D007632:Keratan Sulfate; D002811:Chondroitinsulfatases; D013429:Sulfatases; D005690:Galactose