title: Mucopolysaccharidosis type VI: a predominantly cardiac phenotype associated with homozygosity for p.R152W mutation in the ARSB gene.
abstract: Mucopolysaccharidosis type VI (MPS VI) is a rare lysosomal, autosomal recessive storage disorder caused by deficient activity of N-acetylgalactosamine-4-sulfatase (ARSB). Approximately, 140 ARSB gene mutations have been identified; however, most are private mutations making genotype-phenotype correlation for most MPS VI patients difficult. The aim of this study was to describe the natural clinical course in patients homozygous for the p.R152W mutation from eight unrelated families. From our database of 70 patients with MPS VI, we selected 10 patients homozygous for the p.R152W mutant allele (median age 27.5 years, range 18-38 years). We performed a cross-sectional observational study characterizing the onset and prevalence of clinical manifestations. First signs of the disease, such as cardiac valve disease, slightly decreased joint range of motion and mild growth retardation, were observed in mid-adolescent years (median 15 years). Within the disease course, the most common clinical feature in all the patients was progressive heart disease of predominantly valve origin leading to symptoms of heart failure. Other typical MPS VI features were subtle and not present in all the patients. Delays up to 23 years (median 8.5 years) intervened between symptom onset and disease diagnosis. Patients homozygous for the p.R152W mutation present a cardiac variant of MPS VI characterized by progressive cardiac valve disease leading to serious cardiac complications including abrupt death due to cardiac failure.
authors: Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland. ajurecka@gmail.com
authors: Agnieszka
authors: A
authors: Jurecka
authors: Ekaterina
authors: E
authors: Zakharova
authors: Loreta
authors: L
authors: Cimbalistiene
authors: Nina
authors: N
authors: Gusina
authors: Anna
authors: A
authors: Kulpanovich
authors: Adam
authors: A
authors: Golda
authors: Violetta
authors: V
authors: Opoka-Winiarska
authors: Ewa
authors: E
authors: Piotrowska
authors: Elena
authors: E
authors: Voskoboeva
authors: Anna
authors: A
authors: Tylki-Szymańska
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003710:Demography; D005060:Europe; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics*; D006351:Heart Valves / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D008297:Male; D009031:Moscow; D009087:Mucopolysaccharidosis VI / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human