[Disease due to lysosomal deposits with differential peculiarities: type II GM1 gangliosidosis]. / Enfermedad por depósito lisosomal con peculiaridades diferenciales: gangliosidosis GM1 tipo II.

TITLE: Enfermedad por deposito lisosomal con peculiaridades diferenciales: gangliosidosis GM1 tipo II.

Enfermedad por depósito lisosomal con peculiaridades diferenciales: gangliosidosis GM1 tipo II / Disease due to lysosomal deposits with differential peculiarities: type II GM1 gangliosidosis

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Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis.

OBJECTIVE: Nonimmune hydrops fetalis (NIHF) is defined by the excessive fluid accumulation in more than one foetal compartments and body cavities because of nonimmune reasons. It has been described that 14 lysosomal diseases may be causative of NIHF. The aim of this study was to design a fast protocol to investigate the most frequent lysosomal diseases that are reported that may cause NIHF. METHOD: We analysed the glycosaminoglycans excretion in the amniotic fluid supernatant and four different lysosomal enzymatic activities in the amniotic cultured cells of the different NIHF amniotic fluids we received. RESULTS: We investigated 30 NIHF cases, using this fast protocol. We detected two cases of NIHF because of lysosomal diseases, which represent 6.6%. We diagnosed one case of mucopolysaccharidosis type VII and one case of Gaucher disease. CONCLUSION: The fast protocol we designed analyses seven of the most frequent lysosomal pathologies that have been described that may cause NIHF, with only five different determinations, which make the analysis of NIHF fast, cost-effective and without need of too much amniotic fluid. We believe this protocol may be useful for the analysis of lysosomal diseases in NIHF.

Mucopolisacaridosis tipo VII: ¿causa infrecuente de hidrops fetal? / Mucopolysaccharidosis VII: an unusual cause of hydrops fetalis?

Presentamos el caso de una gestante en la cual se lleva a cabo el diagnóstico de hidrops fetal, a las 17 semanas de embarazo, en dos gestaciones consecutivas. Descartada la etiología inmune, en la segunda gestación se investigó -entre otras- la asociación con enfermedades de depósito lisosomal, detectándose actividad disminuida de la beta-glucuronidasa en amniocitos cultivados y perfil de glucosaminoglucanos en líquido amniótico, indicativos de enfermedad de Sly o mucopolisacaridosis tipo VII, de herencia autosómica recesiva (AU)

We report the case of a pregnant woman who was diagnosed with hydrops fetalis at 17 weeks in two consecutive pregnancies. Once an immune origin was ruled out, the association with lysosomal storage diseases was investigated during the second pregnancy. This showed decreased activity of beta-glucuronidase in cultured cells and a glycosaminoglycan profile in amniotic fluid, indicative of Sly disease or mucopolysaccharidosis type VII which is inherited in an autosomal recessive pattern (AU)

Diagnóstico, biomarcadores y alteraciones bioquímicasde la enfermedad de Gaucher / Diagnosis, biomarkers and biochemical alterations in Gaucher's disease

La enfermedad de Gaucher (EG) es una enfermedad metabólica hereditaria debida al déficit de actividad de la enzima beta-glucocerebrosidasa. El diagnóstico de la EG habitualmente se realiza mediante el análisis fluorimétrico de la enzima beta-glucocerebrosidasa. También se puede realizar midiendo la actividad por espectrometría de masas en tándem. Esta enzima se puede analizar en diferentes materiales como leucocitos, fibroblastos cultivados, sangre seca sobre papel y, en caso del diagnóstico prenatal, en vellosidades coriales o en amniocitos cultivados. Se han descrito distintos biomarcadores para el seguimiento de la EG una vez diagnosticada, para evaluar la respuesta a posibles tratamientos. La actividad quitotriosidasa es el biomarcador más utilizado para la evaluación de la EG y, en caso de pacientes homocigotos para variantes nulas del gen CHIT1, en general, se sustituye por el análisis del biomarcador CCL18 (AU)

Gaucher’s disease (GD) is an inherited metabolic disease due to lack of activity of the enzyme betaglucocerebrosidase. The diagnosis of GD is usually performed by fluorimetric analysis of the enzyme betaglucocerebrosidase. It can also be done by measuring the activity of tandem mass spectrometry. This enzyme can be analyzed in different samples such as leukocytes, fibroblasts, blood dried on paper and in case of prenatal diagnosis in chorionic villi or culture of amniocytes. Various biomarkers have been described for monitoring GD once diagnosed, to evaluate the response to potential treatments. Chitotriosidase activity is the most widely used biomarker for the assessment of GD, and for patients homozygous for the null CHIT1 gene variants, in general, is replaced by the analysis of the biomarker CCL18 (AU)

[Diagnosis, biomarkers and biochemical alterations in Gaucher's disease]. / Diagnóstico, biomarcadores y alteraciones bioquímicasde la enfermedad de Gaucher.

Gaucher's disease (GD) is an inherited metabolic disease due to lack of activity of the enzyme betaglucocerebrosidase. The diagnosis of GD is usually performed by fluorimetric analysis of the enzyme betaglucocerebrosidase. It can also be done by measuring the activity of tandem mass spectrometry. This enzyme can be analyzed in different samples such as leukocytes, fibroblasts, blood dried on paper and in case of prenatal diagnosis in chorionic villi or culture of amniocytes. Various biomarkers have been described for monitoring GD once diagnosed, to evaluate the response to potential treatments. Chitotriosidase activity is the most widely used biomarker for the assessment of GD, and for patients homozygous for the null CHIT1 gene variants, in general, is replaced by the analysis of the biomarker CCL18.

Molecular analysis in Fabry disease in Spain: fifteen novel GLA mutations and identification of a homozygous female.

Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A gene (GLA). Here we report molecular studies in 22 unrelated Spanish patients with Fabry disease ( 20 males and two females). Fifteen novel mutations were identified. In addition 7 previously described mutations and two previously reported polymorphisms were detected. The 15 novel mutations comprise: eight missense E48K (c.142G>A), W81S (c.242G>C), D170H (c.508G>C), W226C (c.678G>T), Q279R (c.836A>G), C382Y (c.1145G>A), I407K (c.1220T>A), L414S (c.1241T>C); one nonsense W95X (c.284G>A); one insertion Y216fsX15 (c.646_647insT); two small deletions G346fsX1 (c.1037delG), K426fsX23 (c.1277_1278delAA); one gross deletion comprising exons 5, 6, 7; one complex mutation (insertion and deletion) A368fsX24 (c.1102delGinsTTATAC), and one splice-site mutation IVS4+1G>A (c.639+1G>A). One of the females was found homozygous for Q279R mutation and she presented with the classic phenotype since the age of 8 years, this case extending into women the severe phenotype observed in classically affected males. Mutation analysis provided precise identification for 30 heterozygotes among female relatives and detection of a de novo mutation. The molecular studies on Spanish Fabry patients here reported further contribute to the identification of new mutations in this disease, and allow reliable detection of heterozygotes which has consequences for genetic counselling and for treatment.