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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 ?-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.

SUBMITTER: Tebani A

PROVIDER: S-EPMC4881565 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series.

Tebani Abdellah A Zanoutene-Cheriet Lahouaria L Adjtoutah Zoubir Z Abily-Donval Lenaig L Brasse-Lagnel Carole C Laquerrière Annie A Marret Stephane S Chalabi Benabdellah Abla A Bekri Soumeya S

International journal of molecular sciences 20160517 5

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, an ...[more]

PMID: 27196898

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Project description:IntroductionBlastocystis sp. is a protozoan that colonizes the gastrointestinal tract of humans and many animals and is currently the most common parasite found in human stools. In some developing countries, its prevalence in study populations may exceed 50%. Morphologically, isolates of Blastocystis sp. found in different hosts are very similar. However, these same isolates show a very high genetic diversity between them and no less than 17 subtypes (or genotypes) have already been identified from molecular data. Genotyping studies have been carried out in many countries around the world and in particular in some Mediterranean countries such as France, spain, Italy, Turkey and Egypt. However, very little genotyping data is available in Algeria. To this end, we conducted the present study to identify and genotype Blastocystis in human and animal stool samples.Patients and methodsOne thousand eight hundred and sixty-nine (1,869) stool samples from kitchen staff as part of the periodic medical check-up, from subjects for the provision of a medical certificate required for the processing of a visa file and from patients with gastrointestinal disorders were examined. In addition to human faeces, animal samples, including 10 poultry, 2 cattle and 2 murine animals were examined. All stools were subjected to direct microscopic examination supplemented by concentration techniques and modified Ziehl Neelsen staining. Molecular characterization of 39 human and 14 animal isolates was performed by sequencing and the resulting sequences compared with those available from GenBank. Sequencing was only contributory for 30 human and 9 animal strains.ResultsOf all human samples examined 284 were positive (15.19%) with a prevalence of 7.38% for Blastocystis. Of the 30 strains that were molecularly characterized, ST3 was predominant (15/30, 50%) followed by ST1 (10/30, 33.33%) and in third place ST2 (4/30, 13.33%). ST4 was identified in only one patient (1/30, 3.33%). The correlation between clinical status and the subtype of Blastocystis identified showed that the number of ST3 was high in asymptomatic subjects (11/15, 73%) compared to symptomatic subjects (4/15, 26.66%), as well as for the ST1 subtype (7/10, 70% versus 3/10, 30%). Conversely, the number of ST2 was higher in subjects with gastrointestinal disorders (3/4, 75%). In addition to human strains, we genotyped 7 avian, 2 murine and 2 bovine strains. Characterization of the avian strains revealed 5 ST6 (71.42%) and 2 ST7 (28, 57%). The murine and bovine strains are identified as ST7 and ST6 respectively.

Project description:BackgroundMucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data.MethodsWe have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease.ResultsWe collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS.ConclusionsMPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy.

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Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series.

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Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series.

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