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A Chabas

Publications and source records attributed to A Chabas.

17 recordsLinked to original sources
PubMed2006

Sudden deterioration in nonclassical infantile-onset Pompe disease responding to alglucosidase alfa infusion therapy: a case report.

A patient with atypical infantile Pompe disease suffered acute respiratory insufficiency at the age of 8 years which resulted in complete immobilization and dependence on assisted ventilation. Shortly after initiation of enzyme replacement therapy, she regained her mobility and, after 20 months of treatment, she now leads an almost normal life with limited restrictions.

Child↗
PubMed2006

Modeling of soiling based on silica-soda-lime glass exposure at six European sites.

Samples of silica-soda-lime float glass, a material selected as a pertinent soiling sensor, were exposed for up to 28 months at four urban sites (Athens, Krakow, London and Prague) and at a semi-urban one (Monte Libretti, near Rome), sheltered from rain. This exhaustive experience permitted to complete and to test the generalisation ability of the results previously obtained on the same material, exposed according to the same protocol, during 24 months, at a single site (Paris). The model previously fitted for the Paris experiment, the Hill equation, could be successfully generalised for four other sites of exposure (Athens, Krakow, Prague and Rome). The analytical form of this model was interpreted in terms of a physical description of the soiling phenomenon. Some of the model coefficients were different from one site to another, depending on the specific environment of exposure (air pollution levels, meteorological factors), while the other ones were rather equivalent. The analysis of the model coefficients, on the one hand, led to an estimation of the period after which soiling is close to its saturation level, and on the other hand, it will permit to correlate these coefficients to the environmental factors, in order to select the most appropriate ones for building dose-response functions for soiling, with broad geographical application.

Journal Article↗
PubMed2000

A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD).

The lysosomal degradation of sphingolipids with short oligosaccharide chains depends on small glycosylated non-enzymatic sphingolipid activator proteins (SAPs, saposins). Four of the five known SAPs, SAP-A, -B, -C and -D, are derived by proteolytic processing from a common precursor protein (SAP-precursor) that is encoded by a gene on chromosome 10 consisting of 15 exons and 14 introns. SAP-B is a non-specific glycolipid binding protein that stimulates in vitro the hydrolysis of about 20 glycolipids by different enzymes. In vivo SAP-B stimulates in particular the degradation of sulphatides by arylsulphatase A. So far, four different point mutations have been identified on the SAP-B domain of the SAP-precursor gene. The mutations result in a loss of mature SAP-B, causing the lysosomal accumulation of sulphatides and other sphingolipids, resulting in variant forms of metachromatic leukodystrophy (MLD). Here we report on a patient with SAP-B deficiency that is caused by a new homoallelic point mutation that has been identified by mRNA and DNA analysis. A 643A > C transversion results in the exchange of asparagine 215 to histidine and eliminates the single glycosylation site of SAP-B. Metabolic labelling experiments showed that the mutation had no effect on the intracellular transport of the encoded precursor to the acidic compartments and its maturation in the patient's cells. All four SAPs (SAP-A to SAP-D) were detectable by immunochemical methods. SAP-B in the patient's cells was found to be slightly less stable than the protein in normal cells and corresponded in size to the deglycosylated form of the wild-type SAP-B. Feeding studies with non-glycosylated SAP-precursor, generating non-glycosylated SAP-B, showed that the loss of the carbohydrate chain reduced the intracellular activity of the protein significantly. The additional structural change of the patient's SAP-B, caused by the change of amino acid 215 from asparagine to histidine, presumably resulted in an almost completely inactive protein.

Child, Preschool↗
PubMed1996

Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype.

Up to now eight patients with alpha-NAGA deficiency have been described. This includes the newly identified patient reported here who died unexpectedly aged 1 1/2 years of hypoxia during convulsions; necropsy was not performed. Three patients have been genotyped previously and here we report the mutations in the other five patients, including two new mutations (S160C and E193X). The newly identified patient is consanguineous with the first patients reported with alpha-NAGA deficiency and neuroaxonal dystrophy and they all had the alpha-NAGA genotype E325K/E325K. Clinical heterogeneity among patients with alpha-NAGA deficiency is extreme. Two affected sibs, homozygotes for E325K, are severely affected and have the signs and symptoms of infantile neuroaxonal dystrophy, but prominent vacuolisation is lacking. The mildly affected patients (two families, three patients) at the opposite end of the clinical spectrum have clear vacuolisation and angiokeratoma but no overt neurological manifestations. Two of them are homozygous for the stop mutation E193X, leading to complete loss of alpha-NAGA protein. These observations are difficult to reconcile with a simple genotype-phenotype correlation and we suggest that factors or genes other than alpha-NAGA contribute to the clinical heterogeneity of the eight patients with alpha-NAGA deficiency. At the metabolic level, the patients with alpha-NAGA deficiency are similar. The major abnormal urinary oligosaccharides are sialylglycopeptides of the O linked type. Our enzymatic studies indicated that these compounds are not the primary lysosomal storage products.

Animals↗
PubMed1996

Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII.

Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. We used reverse-transcription-PCR-SSCP and direct sequencing to screen for mutations in the human beta-glucuronidase cDNA of 17 MPS VII patients with severe presentation of the disease. Mutations resulting in an unstable mRNA were detected in genomic DNA with direct sequencing of the PCR-amplified beta-glucuronidase exons. We found extensive genetic heterogeneity in MPS VII alleles: in addition to 6 or 12 previously reported mutations (L176F, R216W, R357X, R382C, W507X, and W627C), we detected 14 undescribed mutations in the beta-glucuronidase coding region that produce MPS VII alleles (G136R, E150K, S312X, Y320S, Y320C, H351Y, R382H, R374C, R435P, R477W, G572D, Y508C, K606N and 1900 delta GA). The mutations in hydropic fetuses were widely scattered in the beta-glucuronidase gene. Analysis of three polymorphic sites of the mutant alleles (1766T/C, 1972C/T and a new 1091+27C/G polymorphism) allowed exclusion of identity by descent for some recurrent mutations. Three of four mutations introducing a premature translation stop codon were found to affect mRNA abundance and/or structure. Expression studies provided evidence for the causal relationship between each of the mutations found in MPS VII alleles and the enzyme deficiency, in that all mutations identified exhibited markedly reduced enzyme activity expressed in COS7 cells following transfection with the mutant cDNA.

Adult↗
PubMed1996

Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant.

Lysosomal degradation of ganglioside GM2 by beta-hexosaminidase A (hex A) requires the presence of the GM2 activator protein (GM2AP) as an essential cofactor. A deficiency of the GM2 activator causes the AB variant of GM2 gangliosidosis, a recessively inherited disorder characterized by excessive neuronal accumulation of GM2 and related glycolipids. Two novel mutations in the GM2 activator gene (GM2A) have been identified by the reverse-transcriptase-PCR method--a three-base deletion, AAG262-264, resulting in a deletion of Lys88, and a single-base deletion, A410, that causes a frameshift. The latter results in substitution of 33 amino acids and the loss of another 24 amino acid residues. Both patients are homoallelic for their respective mutations inherited from their parents, who are heteroallelic at the GM2A locus. Although the cultured fibroblasts of both patients produce normal levels of activator mRNA, they lack a lysosomal form of GM2AP. Pulse/chase labeling of cultured fibroblasts of the patients, in presence and absence of brefeldin A, indicates a premature degradation of both--mutant and truncated--GM2APs in the endoplasmic reticulum or Golgi. These results were supported by in vitro translation experiments and expression of the mutated proteins. When the mutated GM2APs were expressed in Escherichia coli, both mature GM2AP forms turned proved to exhibit only residual activities in an in vitro assay.

Adult↗
PubMed1995

A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene.

We present evidence that a 480G-->A transition in the coding region of the beta-glucuronidase gene, which results in an aspartic-acid-to-asparagine substitution at amino acid position 152 (D152N), produces a pseudodeficiency allele (GUSBp) that leads to greatly reduced levels of beta-glucuronidase activity without apparent deleterious consequences. The 480G-->A mutation was found initially in the pseudodeficient mother of a child with mucopolysaccharidosis VII (MPSVII), but it was not on her disease-causing allele, which carried the L176F mutation. The 480G-->A change was also present in an unrelated individual with another MPSVII allele who had unusually low beta-glucuronidase activity, but whose clinical symptoms were probably unrelated to beta-glucuronidase deficiency. This individual also had an R357X mutation, probably on his second allele. We screened 100 unrelated normal individuals for the 480G-->A mutation with a PCR method and detected one carrier. Reduced beta-glucuronidase activity following transfection of COS cells with the D152N cDNA supported the causal relationship between the D152N allele and pseudodeficiency. The mutation reduced the fraction of expressed enzyme that was secreted. Pulse-chase experiments indicated that the reduced activity in COS cells was due to accelerated intracellular turnover of the D152N enzyme. They also suggested that a potential glycosylation site created by the mutation is utilized in approximately 50% of the enzyme expressed.

Alleles↗
PubMed1991

Low beta-glucuronidase activity in a healthy member of a family with mucopolysaccharidosis VII.

A phenotypically normal mother of a mucopolysaccharidosis VII child, is reported with an unusually low beta-glucuronidase activity. Low enzyme activity was systemic (6-10% of controls) and residual beta-glucuronidase in leukocytes had an apparently normal Km value. [35S]sulphate incorporation and chase assays in fibroblasts gave values similar to control cells. A normal excretion pattern of glycosaminoglycan was found in this woman's urine. Low enzymatic activity can be related to a non-pathological 'pseudodeficiency' allele for beta-glucuronidase; this woman appears to be an apparent compound heterozygote for this allele and mucopolysaccharidosis VII. Her next pregnancy was monitored by chorionic villus sampling and a heterozygous fetus was suspected. These studies stress the need for complete enzyme investigations of obligate carriers for mucopolysaccharidoses in order to prevent difficulties at prenatal analysis.

Cells, Cultured↗
PubMed1987

[Mucolipidosis II or "I-cell disease" in the newborn infant. 2 new cases].

Clinical and biochemical findings of two patients with neonatal mucolipidosis II are presented. Characteristic coarse facial features, shortness of stature, psychomotor retardation and vacuolated lymphocytes were observed in both cases. However, in one case symptoms presentation was earlier and course of the disease was markedly more severe, with death occurring at the age of 3 months. Biochemically similar increase of serum multiple lysosomal enzymes and decrease of fibroblast activities was demonstrated in both patients. Authors have found elevations of some acid hydrolases in sera from parents (obligate heterozygotes) of both patients and in individuals from two more families also obligated carries.

Humans↗
PubMed1977

[Fucosidosis type 2. A new case (author's transl)].

We have studied a child 10 years old with a defficit of alpha-fucosidase demonstrated in the urine, serum, tears and fibroblasts culture. The clinical evolution and the presence of a "angiokeratom corporis diffusum" permits one to diagnose the patient in the type 2 fucosidosis. We have revised the clinical features, the exigible criteria for biochemical diagnosis, the histopathological findings, ultrastructural alterations and the genetic aspects; specially the behaviour of the H substance and Lewis in the red cell and saliva.

Biopsy↗