title: Hunter syndrome (Muccopolysaccharridosis Type II) in Macedonia and Bulgaria.
abstract: BACKGROUND
  Mucopolysaccharidosis II (MPS II) is caused by a deficiency of iduronate-2-sulfatase (IDS; EC 3.1.6.13).
  
  
  RESULTS
  We describe 11 boys from Bulgaria and Macedonia detected in the period from 1998 to 2008. The mean age at diagnosis was 4.77+/-1.29 years. All children were severely retarded: IQ ranged from 34-80, and they all had coarse faces and hepatomegaly. In addition, splenomegaly was found in 81.81% patients, dysostosis in 45.45%, kyphosis in 27.27%, deafness in 18.08%, growth below the third percentile in 45.45%, growth below the parental target height in all patients, stiff joints in 56.56% and hypertrophic myocardiopathy in 18.18% children. Two patients died at the age of 11 and 35 years. Plasma iduronate-2-sulfatase was low in all probands and normal in parents and relatives. Two new mutations were discovered: p.K236N (c.708G>C) in a child with a moderately severe phenotype, and p.Q80K (c.238C>A) which resulted in a severe phenotype and early death at the age of 11 years. Heterozygote carriers of the pathogenic allele were 29 female relatives. The calculated incidence rate for MPS II in Macedonia (censuses 1994 and 2002, children under 14 years: 483,923 and 426,280) and Bulgaria (censuses 1992 and 2006, children under 14 years: 1 126, 598 and 1,077,020) are 0.36 and 0.46 respectively, while the calculated prevalence rate are 3.6 and 4.6 per 1,000,000 boys (aged 0-14 years). Correlating phenotype and genotype remains a complex endeavour.
  
  
  CONCLUSIONS
  We report calculated incidence and prevalence rates in two South Eastern European countries, and 2 novel genetic alterations correlated with their phenotypes.
authors.affiliation: University Children's Hospital, Medical School, Skopje, R. Macedonia.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Gucev
authors.forename: V
authors.initials: V
authors.lastname: Tasic
authors.forename: I
authors.initials: I
authors.lastname: Sinigerska
authors.forename: I
authors.initials: I
authors.lastname: Kremensky
authors.forename: R
authors.initials: R
authors.lastname: Tincheva
authors.forename: N
authors.initials: N
authors.lastname: Pop-Jordanova
authors.forename: D
authors.initials: D
authors.lastname: Danilovski
authors.forename: D
authors.initials: D
authors.lastname: Hofer
authors.forename: E
authors.initials: E
authors.lastname: Paschke
mesh_terms: D000293:Adolescent; D000328:Adult; D002031:Bulgaria / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D016532:Mucopolysaccharidosis II / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D009154:Mutation; D018843:Republic of North Macedonia / Q000453:epidemiology
chemical_list: D006023:Glycoproteins; C018322:IDS protein, human