RESUMEN
BACKGROUND: Growing evidence suggests that hypovitaminosis D contributes to the pathogenesis of multiple sclerosis (MS). OBJECTIVE: This study aimed to evaluate whether vitamin D levels are associated with having MS and some of its characteristics in the Moroccan population. METHODS: Using liquid chromatography-tandem mass spectrometry, the 25(OH)D3 metabolite was measured to quantify vitamin D serum levels (DSLs) in 113 patients with MS and 146 healthy controls matched for gender and age. DSLs were then compared between patients and controls, with correlations sought between DSLs and gender, age at onset, disease duration, MS type, degree of disability (EDSS score) and disease severity (MSSS) in patients. RESULTS: Hypovitaminosis D (DSL<30ng/mL) was observed in 97.3% of MS patients and in 98.6% of controls. Although the mean DSL was slightly lower in patients (11.69±6.97ng/mL) than in controls (12.98±6.58ng/mL), there was no significant association between DSL and MS status (P=0.131). Similarly, among patients, no apparent association was found between DSL and MS type (P=0.214), EDSS score (P=0.076) or MSSS (P=0.772). CONCLUSION: Our study suggests that DSL is not associated with having MS nor with MS type, degree of disability or disease severity in the Moroccan population. On the other hand, DSL was lower in women and decreased with age.
Asunto(s)
Esclerosis Múltiple/sangre , Estado Nutricional , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adulto , Edad de Inicio , Envejecimiento , Calcifediol/sangre , Estudios de Casos y Controles , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Esclerosis Múltiple/complicaciones , Valores de Referencia , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
BACKGROUND: Mutilating sensory neuropathy with spastic paraplegia is a very rare disease with both autosomal dominant and recessive modes of inheritance. We previously mapped the locus of the autosomal recessive form to a 25 cM interval between markers D5S2048 and D5S648 on chromosome 5p. In this candidate interval, the Cct5 gene encoding the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (CCT) was the most obvious candidate gene since mutation in the Cct4 gene encoding the CCT delta subunit has been reported to be associated with autosomal recessive mutilating sensory neuropathy in mutilated foot (mf) rat mutant. METHODS: A consanguineous Moroccan family with four patients displaying mutilating sensory neuropathy associated with spastic paraplegia was investigated. To identify the disease causing gene, the 11 coding exons of the Cct5 gene were screened for mutations by direct sequencing in all family members including the four patients, parents, and six at risk relatives. RESULTS: Sequence analysis of the Cct5 gene revealed a missense A492G mutation in exon 4 that results in the substitution of a highly conserved histidine for arginine amino acid 147. Interestingly, R147 was absent in 384 control matched chromosomes tested. CONCLUSION: This is the first disease causing mutation that has been identified in the human CCT subunit genes; the mf rat mutant could serve as an animal model for studying these chaperonopathies.
Asunto(s)
Chaperoninas/genética , Neuropatía Hereditaria Motora y Sensorial/genética , Chaperonas Moleculares/genética , Mutación Missense , Paraplejía Espástica Hereditaria/genética , Secuencia de Aminoácidos , Chaperonina con TCP-1 , Chaperoninas/química , Análisis Mutacional de ADN , Exones , Femenino , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Humanos , Masculino , Chaperonas Moleculares/química , Datos de Secuencia Molecular , Linaje , Subunidades de Proteína/química , Subunidades de Proteína/genética , Alineación de Secuencia , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnósticoRESUMEN
Spinal muscular atrophy (SMA) is an autosomal recessive motor neuropathy characterized by selective degeneration of anterior horn cells of the spinal cord. Childhood SMA is divided into three types (I-III) on the basis of age of onset and severity. These disorders have been linked to the 5q13 region, where mutations in the Survival Motor Neuron 1 (SMN1) gene have been found in affected individuals. In the case of adult-onset SMA (type IV), on the other hand, reports of homozygous absence of SMN1 gene have been rare. We conducted deletion analysis of SMN and a neighboring gene, NAIP (neuronal apoptosis inhibiting protein). Among 54SMA patients (types I-IV), all of Moroccan origin, Exon 7 of the SMN1 gene was homozygously absent in 100% of type I, 90% of type II, 74% of type III and 80% of type IV SMA patients. Deletion of SMN1 exon 8 was detected in 100% of type I, 53% of type II, 53% of type III and 80% of type IV patients. NAIP exon 5 was homozygously deleted in 67% of type I, 32% of type II, 5% of type III and 20% of type IV SMA patients. Thirty control individuals who were studied had normal SMN1 and NAIP genes. Our results show a high incidence of SMN1 gene deletion in adult-onset SMA patients indicating that SMN1 is the autosomal recessive adult SMA-causing gene. While NAIP is commonly deleted in SMA, this is unlikely to affect disease severity; it was deleted in two adult SMA patients with mild phenotypes.
Asunto(s)
Eliminación de Gen , Atrofia Muscular Espinal/genética , Proteínas del Tejido Nervioso/genética , Adulto , Edad de Inicio , Anciano , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Marruecos , Atrofia Muscular Espinal/patología , Fenotipo , Reacción en Cadena de la Polimerasa , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Índice de Severidad de la Enfermedad , Proteína 1 para la Supervivencia de la Neurona MotoraRESUMEN
Vitamin E is one of the most important lipid-soluble antioxidant nutrient. Severe vitamin E deficiency (VED) can have a profound effect on the central nervous system. VED causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. We report here a patient presenting this syndrome, but also a prolactin and FSH adenoma. Both the neurological syndromes and the adenoma regressed after treatment with alpha-tocopherol. Although, the presence of the prolactinoma in this patient may not be related to his vitamin E deficiency, alpha-tocopherol treatment seems to be beneficial and might usefully be tested in patients with hypophyseal secreting other forms of adenoma.