[Hereditary juvenile cobalamin deficiency due to mutations in GIF gene]. / Déficit de cobalamina hereditario juvenil causado por mutaciones en el gen GIF.

Inborn errors of cobalamin (Cbl) metabolism affect its absorption, transport, as well as its intracellular metabolism. Hereditary juvenile megaloblastic anaemia due to cobalamin deficiency, results from defects in Cbl absorption. There is a lack of vitamin B12 in congenital pernicious anaemia due to intrinsic factor deficiency and megaloblastic anaemia 1 due to selective intestinal malabsorption of vitamin B12 or Imerslund-Gräsbeck syndrome. Differential diagnosis can't be accomplished only by clinical and biochemical findings. We present a patient from Spain with a megaloblastic anaemia due to intrinsic factor deficiency (IFD). The patient is a compound heterozygous in GIF gene for a splice site mutation inherited from his mother and a missense change inherited from his father. The identification of disease-causing mutations in specific genes has improved our ability to diagnose many of these conditions.

[Prader-Willi and Angelman syndromes: 21 years of experience]. / Síndromes de Prader-Willi y de Angelman. Expriencia de 21 años.

INTRODUCTION: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) were the first syndromes in humans that were known to originate from the phenomenon of the genomic imprinting. We review our experience of 21 years with PWS and AS that were confirmed with the genetically. RESULTS: Of the 13,875 patients recorded during the study period, 11 were diagnosed with PWS (18%), 7 males (63.6%) and 4 females (36.4%), with a mean age of 9.06 years (+/- 6.92, range: 0.68-21.6). The time of the follow up of this group was 3.83 years (+/- 4.03, range: 0.49-15.3), and the age at diagnosis was 4.4 years (+/- 6.84, range: 0.03-19.38). Almost three quarters (72.7% of the PWS patients had a uniparental dysomy and 27.3% a paternal deletion. Six patients (8%) were diagnosed with AS, 4 females (66.6%) and 2 males (33.4%), with a mean age of 14.65 years (+/- 11.89, range: 1.3-30.7). The time of follow up was 6.76 years (+/- 5.89,range: 0.16-15), and the age at diagnosis was 8.84 years (+/- 9.11, range: 1.10-23). A maternal deletion was present in 83.3% of the AS patients and 16.7% had a maternal dysomy. DISCUSSION: As genetic advances are made these pathologies are confirmed before. Unlike the data in the literature, in our series most patients diagnosed with PWS (72'3%) had uniparental disomy. Recent studies correlation genotype with phenotype, in PWS is more serious if it occurs a deletion and in SA is milder in the case of uniparental disomy. CONCLUSIONS: Genetic studies must be performed in view of the established clinical symptoms: neonatal hypotonia of unknown cause in PWS and psychomotor deficits with autism features, particularly associated with epilepsy, must be evaluated in AS to prevent diagnostic uncertainties, unnecessary complementary examinations and to provide early genetic counselling.

[Myotonic dystrophy. 18 years experience in a neuropaediatric clinic]. / Distrofia miotónica. Nuestra experiencia de 18 años en consulta de Neuropediatría.

INTRODUCTION: Myotonic dystrophy is a highly variable autosomic dominant inherited multisystemic disease. We review our 18 years experience with patients suffering from this disease. RESULTS: Eleven patients were identified following a molecular genetic study: 2 patients died, 5 are still under control, 2 are being controlled in another Centre, and 3 dropped out. Three of them were relatives. Seven newborns started with hypotonic symptoms in the neonatal period, with hypotonic symptoms, of which 4 had foetal suffering. One child was diagnosed at age of 3 due to her father being affected. One girl was seen at age of 10 due to stiffness and tightening of her hands for years. One boy, aged 5, was examined due to abnormal hands posture, and a 4 year old child due to psychomotor delay. Associated disorders: 7 children with psychomotor delay, 2 cases of cataracts, 1 case of diabetes type I, 3 cases of hypercholesterolemia, 1 abdominal sarcoma, 1 case of femur and hip fracture, 2 cases of interatrial communication. The diagnostic was made in 5 cases by a clinic due to mother-son relation phenotype, in 3 cases after the family diagnosis and in another 3 cases non-congenital symptoms exclusively in the child's clinic. DISCUSSION: In our experience, myotonic dystrophy is uncommon; it is often congenital, and is associated with perinatal suffering. Genetics can identify or exclude the process. This must be done on newborns who are hypotonic for an unknown reason. It should be suspected in a child who presents with motor abnormalities in the fingers and hands.

Hiperhomocisteinemia y mutación C677T de la metilentetrahidrofolato reductasa / Hyperhomocysteinemia and C677T methylentetrahydrofolate reductase mutation

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Déficit de cobalamina hereditario juvenil causado por mutaciones en el gen GIF / Hereditary juvenile cobalamin deficiency due to mutations in GIFgene

Los errores congénitos del metabolismo de la cobalamina afectan a su absorción, transporte o metabolismo intracelular. La anemia megaloblástica hereditaria juvenil por déficit de vitamina B12 está causada por una malabsorción de cobalamina. En la anemia perniciosa congénita por déficit de factor intrínseco, y en la anemia megaloblástica 1 por malabsorción de vitamina B12, causada por un defecto en el receptor vitamina B12/factor intrínseco o síndrome de Imerslund-Gräsbeck, existe un déficit de vitamina B12. El diagnóstico diferencial entre estas dos entidades no puede ser completado únicamente mediante la clínica y los datos de laboratorio. Presentamos un paciente español con anemia megaloblástica hereditaria juvenil por déficit de factor intrínseco, heterocigoto compuesto para dos mutaciones distintas en el gen GIF. La identificación de mutaciones causantes de la enfermedad en genes específicos ha mejorado nuestra capacidad de diagnóstico y tratamiento de estas situaciones (AU)

Inborn errors of cobalamin (Cbl) metabolism affect its absorption, transport, as well as its intracellular metabolism. Hereditary juvenile megaloblastic anaemia due to cobalamin deficiency, results from defects in Cbl absorption. There is a lack of vitamin B12 in congenital pernicious anaemia due to intrinsic factor deficiency and megaloblastic anaemia 1 due to selective intestinal malabsorption of vitamin B12 or Imerslund-Gräsbeck syndrome. Differential diagnosis can't be accomplished only by clinical and biochemical findings. We present a patient from Spain with a megaloblastic anaemia due to intrinsic factor deficiency (IFD). The patient is a compound heterozygous in GIF gene for a splice site mutation inherited from his mother and a missense change inherited from his father. The identification of disease-causing mutations in specific genes has improved our ability to diagnose many of these conditions (AU)

Influencia de factores bioquímicos y genéticos en las concentraciones de homocisteína / Influence of biochemical and genetic factors on homocysteine concentrations

Antecedentes En varios estudios se ha analizado la asociación entre el genotipo del gen metilentetrahidrofolato reductasa (MTHFR) y las concentraciones de homocisteína plasmática, pero muy pocos estudios se han realizado en niños. Objetivo Determinar la concentración plasmática de homocisteína total, ácido fólico, folato intraeritrocitario (FCR) y vitamina B12 en un grupo de niños sanos y ver su posible relación con el genotipo MTHFR. Sujetos y métodos Formaron parte del estudio 83 participantes (45 chicos y 38 chicas) de edad comprendida entre 1 semana y 18 años. Las muestras de plasma y sangre completa se almacenaron a -80 °C para su posterior determinación de los parámetros bioquímicos y moleculares. La determinación de homocisteína total se realizó mediante ensayo de inmunofluorescencia polarizada; mientras que la concentración sérica de ácido fólico, folato intraeritrocitario y vitamina B12 se determinó mediante inmunoanálisis electroquimioluminiscente. El análisis molecular se realizó mediante reacción en cadena de la polimerasa (PCR), y posterior digestión enzimática, del ADN obtenido de las muestras de sangre. Resultados Las concentraciones plasmáticas de homocisteína se correlacionaron negativamente con las de ácido fólico, vitamina B12 y FCR, pero positivamente con la edad (p < 0,005).Se ha encontrado una interacción entre la edad-genotipo MTHFR y las concentraciones de ácido fólico, vitamina B12 y FCR, pero no con las concentraciones de homocisteína. Conclusiones Nuestras observaciones sugieren que la concentración de homocisteína en la población pediátrica sana está más influida por factores bioquímicos como el ácido fólico, que genéticos (AU)

Determinantes de la concentración de homocisteína plasmática. Réplica / Determinants of plasma homocysteine concentration. Reply

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