Attenuated osteoarticular phenotype of type VI mucopolysaccharidosis: a report of four patients and a review of the literature.
Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI, OMIM 253200) is caused by mutations in the gene coding for N-acetylgalactosamine-4-sulfatase (4-sulfatase, arylsulfatase B, ARSB, EC 3.1.6.12), a lysosomal enzyme involved in the degradation of dermatan sulfate (DS). The clinical presentation of MPS VI varies greatly with respect to age of onset and rate of disease progression. This report focuses on the attenuated form of MPS VI, which can go unrecognized for years and often presents with atypical signs or symptoms. We described a cohort of MPS VI patients (n = 4) heterozygous for the p.Y210C mutation who had a significant osteoarticular involvement at the onset of their disease and who were diagnosed years or even decades later. We have also reviewed the literature (n = 36). Two types of attenuated MPS VI phenotypes could be distinguished: osteoarticular and cardiac. The majority of MPS VI patients reported so far as relatively attenuated presented with an essentially osteoarticular phenotype associated with the p.Y210C mutation. Patients homozygous for the p.R152W mutation presented with a cardiac phenotype, which, despite fulfilling the generally used criteria for attenuated phenotype, may lead to fast disease progression and abrupt death. The knowledge of natural history and genotype-phenotype correlation may help in developing a tailored therapy potentially using enzyme replacement therapy with substrate reduction therapy or chaperones.
Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland, ajurecka@gmail.com.
Agnieszka
A
Jurecka
Ekaterina
E
Zakharova
Vera
V
Malinova
Elena
E
Voskoboeva
Anna
A
Tylki-Szymańska
D000483:Alleles; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D056947:Enzyme Replacement Therapy; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D009154:Mutation; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D016896:Treatment Outcome
D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human