A novel compound mutation in alpha-L-iduronidase gene causes mucopolysaccharidosis type

Mucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused bymutations in alpha-L-iduronidase (IDUA) gene. IDUA contributes to the degradation of the glycosaminoglycans, including heparan sulphate and dermatan sulphate. Deficient activity of IDUA generates accumulation of glycosaminoglycans in lysosomes leading to MPS I. Here, we identified twoboys with MPS I caused by a compound heterozygote of a reported c.265C > T (p.R89W) missense mutation in exon 2 and a novel c.1633G > T (p.E545*, 109) nonsense mutation in exon 11 of IDUA gene in a Chinese family. R89 is close to the active site and its replacement will affect the structure and function of IDUA. Besides, termination from E545 deletes one of the prominent domainsand alters the spatial structure of IDUA. In conclusion, our study demonstrates a previously unrecognized mutation in IDUA gene and this report adds to the mutational spectrum observed.

Mutation c.1190-1delG/N in intron 8 and c.1708G>C/N in exon 12 not reported in the IDUA gene developed a clinical phenotype of Scheie syndrome / Mutación c.1190-1delG/N en el intrón 8 y c.1708G>C/N en el exón 12 no reportada en el gen de IDUA desarrolló un fenotipo clínico de síndrome de Scheie

Mucopolysaccharidoses are a group of lysosomal storage disorders caused by deficiency of enzymes catalyzing the degradation of glycosaminoglycans. Mucopoly-saccharidosis I can present a wide range of phenotypic characteristics with three major recognized clinical entities: Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression. These are caused by the deficiency or absence of α-L-iduronidase, essential to the metabolism of both dermatan and heparan sulfate, and it is encoded by the IDUA gene. We report the case of a 34-year-old male patient with enzymatic deficiency of α-L-iduronidase, accumulation of its substrate and a previously unreported mutation in the IDUA gene that developed a phenotype of Scheie syndrome.

Las mucopolisacaridosis son un grupo de trastornos de almacenamiento lisosomal causada por la deficiencia de enzimas que catalizan la degradación de glicosaminoglicanos. La mucopolisacaridosis tipo I puede presentar un amplio rango de características fenotípicas englobadas en tres entidades clínicas reconocidas: los síndromes de Hurler y Scheie representan los fenotipos graves y leves del espectro clínico, respectivamente y el síndrome de Hurler-Scheie intermedio en la expresión fenotípica. Estos son causados por la deficiencia o ausencia de la α-L-iduronidasa esencial para el metabolismo del dermatán y el heparán sulfato y es codificada por el gen IDUA. Se presenta el caso de paciente masculino de 34 años de edad con deficiencia enzimática de α-L-iduronidasa, acumulación de su sustrato y una mutación en el gen IDUA, no reportada previamente, que desarrolló un fenotipo del síndrome de Scheie.