No evidence that polymorphisms of the vanishing white matter disease genes are risk factors in multiple sclerosis.

Febrile infections are known to cause exacerbations in the white matter disorders 'vanishing white matter' (VWM) and multiple sclerosis (MS). We hypothesized that polymorphisms in EIF2B1-5, the genes involved in VWM, might be risk factors for the development of MS or temperature sensitivity in patients with MS. We found no difference in the frequencies of 15 EIF2B1-5 variants between patients with MS and healthy controls, and none of the variants showed significant deviation of the Hardy-Weinberg equilibrium. Furthermore, sequencing data of EIF2B1-5 in 20 patients with MS and measurement of the activity of eIF2B complex in patient-derived lymphoblasts did not support our hypothesis.

Vacuolating megalencephalic leucoencephalopathy: 24 years follow-up of two siblings

La leucoencefalopatía megalencefálica con quistes subcorticales (MLC) es un trastorno de herencia autosómica recesiva de curso progresivo crónico. El gen MLC1 ha sido localizado en el cromosoma 22qtell y ya han sido descritas 26 mutaciones diferentes. Presentamos dos hermanas, hijas de padres no consanguíneos con las características propias de la MLC. Las dos mostraban macrocefalia desde los primeros meses de vida. Tras un corto tiempo se observó en ellas torpeza motora, ataxia, crisis y retraso psicomotor. Durante la niñez ambas presentaron estado de coma que duró algunos días tras un trauma craneal de poca importancia. La hermana mayor experimentó deterioro permanente del cuadro clínico durante la edad adulta. La epilepsia y las alteraciones en el electroencefalograma eran crónicas, tendiendo a mejorar en la edad adulta. La biopsia cerebral mostró normalidad o cambios menores en la sustancia gris cortical, mientras que en la sustancia blanca existía gliosis, aumento de los espacios extracelulares y disminución del número de fibras con finas vainas de mielina. Hemos seguido a las pacientes durante 24 años, desde que tenían 4 y 8 años, respectivamente, hasta la actualidad en que tienen 28 y 32 años. El seguimiento clínico y de neuroimagen mostró un curso crónico con progresión más acentuada de las anormalidades en la sustancia blanca que en la expresividad clínica. Se encontró en las dos hermanas una mutación homozigótica del gen MLC1. La hermana mayor, de 32 años, necesita silla de ruedas para moverse, pero contacta bien con la familia y la gente de su entorno. La joven, de 28 años, muestra una discreta ataxia, espasticidad y torpeza motora, pero puede participar en las actividades comunes de la vida diaria

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder with a chronic progressive course. The gene, MLC1, has been localized on chromosome 22qtell and 26 different mutations have been described. We report two siblings of non-consanguineous parents who presented with characteristic features of MLC. They showed macrocephaly from the first months of life. After a short time, motor clumsiness, ataxia, seizures and psychomotor retardation were observed. During childhood, both patients had a coma that lasted several days following a minor head trauma. The eldest sister experienced a permanent deterioration of the clinical picture after the coma. Epilepsy and electroencephalographic alterations were chronic, tending to improve during adulthood. Cerebral biopsy showed normal or minor changes in the cortical grey matter, and in the white matter gliosis, increased extracellular spaces and decreased numbers of fibres with thin myelin sheets . We have followed the patients during 24 years, from the ages of 4 and 8 years to the their present ages of 28 and 32 years. Clinical and neuro-imaging follow-up showed a chronic course with more prominent progression of the white matter abnormalities than of the neurological features. A homozygous mutation of the MLC1 gene was found in both siblings. The eldest patient, 32 years-old, needs a wheel-chair but has a good contact with the family and surroundingpeople. The youngest, 28-years-old, shows mild ataxia, spasticity and motor clumsiness, but she is able to participate in activities of daily life