title: Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series.
abstract: Mucopolysaccharidoses (MPS's) represent a subgroup of lysosomal storage diseases related to a deficiency of enzymes that catalyze glycosaminoglycans degradation. Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by a deficiency of α-l-iduronidase encoded by the IDUA gene. Partially degraded heparan sulfate and dermatan sulfate accumulate progressively and lead to multiorgan dysfunction and damage. The aim of this study is to describe the clinical, biochemical, and molecular characteristics of 13 Algerian patients from 11 distinct families. MPS I diagnosis was confirmed by molecular study of the patients' IDUA gene. Clinical features at the diagnosis and during the follow-up are reported. Eighty-four percent of the studied patients presented with a mild clinical phenotype. Molecular study of the IDUA gene allowed the characterization of four pathological variations at the homozygous or compound heterozygote status: IDUA NM_00203.4:c.1598C>G-p.(Pro533Arg) in 21/26 alleles, IDUA NM_00203.4:c.532G>A-p.(Glu178Lys) in 2/26 alleles, IDUA NM_00203.4:c.501C>G-p.(Tyr167*) in 2/26 alleles, and IDUA NM_00203. 4: c.1743C>G-p.(Tyr581*) in 1/26 alleles. This molecular study unveils the predominance of p.(Pro533Arg) variation in our MPS I patients. In this series, the occurrence of some clinical features linked to the Scheie syndrome is consistent with the literature, such as systematic valvulopathies, corneal opacity, and umbilical hernia; however, storage signs, facial dysmorphic features, and hepatomegaly were more frequent in our series. Screening measures for these debilitating diseases in highly consanguineous at-risk populations must be considered a priority health problem.
authors.affiliation: Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76031, France. abdellah.tebani@chu-rouen.fr.|Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen 76031, France. abdellah.tebani@chu-rouen.fr.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Tebani
authors.affiliation: Department of Pediatrics, Oran University Hospital, Oran 31000, Algeria. houaria26dz@yahoo.fr.
authors.forename: Lahouaria
authors.initials: L
authors.lastname: Zanoutene-Cheriet
authors.affiliation: Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76031, France. zoubir.adjtoutah@jsbio.fr.
authors.forename: Zoubir
authors.initials: Z
authors.lastname: Adjtoutah
authors.affiliation: Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen 76031, France. lenaig.abily-donval@chu-rouen.fr.|Department of Neonatal Pediatrics and Intensive Care, Rouen University Hospital, Rouen 76031, France. lenaig.abily-donval@chu-rouen.fr.
authors.forename: Lenaig
authors.initials: L
authors.lastname: Abily-Donval
authors.affiliation: Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76031, France. carole.lagnel@univ-rouen.fr.|Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen 76031, France. carole.lagnel@univ-rouen.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Brasse-Lagnel
authors.affiliation: Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen 76031, France. annie.laquerriere@chu-rouen.fr.|Pathology Laboratory, Rouen University Hospital, Rouen 76031, France. annie.laquerriere@chu-rouen.fr.
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.affiliation: Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen 76031, France. stephane.marret@chu-rouen.fr.|Department of Neonatal Pediatrics and Intensive Care, Rouen University Hospital, Rouen 76031, France. stephane.marret@chu-rouen.fr.
authors.forename: Stephane
authors.initials: S
authors.lastname: Marret
authors.affiliation: Department of Pediatrics, Oran University Hospital, Oran 31000, Algeria. ab_chalabi@yahoo.fr.
authors.forename: Abla
authors.initials: A
authors.lastname: Chalabi Benabdellah
authors.affiliation: Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76031, France. Soumeya.bekri@chu-rouen.fr.|Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen 76031, France. Soumeya.bekri@chu-rouen.fr.
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
mesh_terms: D000293:Adolescent; D000462:Algeria; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000235:genetics*; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D055815:Young Adult
chemical_list: D001120:Arginine; D011392:Proline; C000615655:IDUA protein, human; D007068:Iduronidase
keywords: GAGs; IDUA; dermatan sulfate; heparin sulfate; mucopolysaccharidosis type I