Early Onset Methylmalonic Aciduria and Homocystinuria cblC Type With Demyelinating Neuropathy

Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of vitamin B 12 (cobalamin) metabolism. The recent cloning of the disease gene, MMACHC, has permitted genotypephenotype correlation. In a 1-year-old girl, compound heterozygous c.271dupA and c.616C>T mutations in MMACHC were identified as causing an early onset methylmalonic aciduria and homocystinuria, cblC type, which was complicated by sensorimotor peripheral demyelinating neuropathy. Ó 2010 by Elsevier Inc. All rights reserved. Frattini D, Fusco C, Ucchino V, Tavazzi B, Della Giustina E. Early onset methylmalonic aciduria and homocystinuria cblC type with demyelinating neuropathy. Pediatr Neurol 2010;43:135-138

Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation

Abstract Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. Most patients with an SPG3A mutation present with a pure phenotype and early-onset disease, although complicated forms with peripheral neuropathy are also reported. We report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy in a 4-year-old girl resembling diplegic cerebral palsy

Disorder of cerebellar foliation in Walker's lissencephaly and neu-laxova syndrome.

A diffuse disorder of cerebellar foliation was found in eight infants and one fetus with Walker's lissencephaly. The cerebellar cortex consisted of fused and irregularly distorted folia. In the white matter, trilaminated rings of cortex were concentrically arranged around blood vessels and mesenchymal tissue. The normal relative position of the different classes of cortical nerve cells was preserved. Cells of the external granular layer invaded the meninges and migrated along penetrating blood vessels. We believe that this foliation disorder is caused by a defect in the external basal lamina that allows adjacent folia to be fused and sulci obliterated by intrameningeal ectopias of external granule layer cells. Physical forces applied during development probably contribute to the distortion of the gyral pattern. There was a volumetric reduction of the neocerebellum, which might also be a consequence of the basal lamina defect. The cerebellum of a fetus with the Neu-Laxova syndrome showed the same abnormalities as in Walker's lissencephaly. It is postulated that these two conditions belong to a class of prenatal developmental disorders that involves a defect of the extracellular matrix

Minimal€ holoprosencephaly in a 14q deletion syndrome patient

We report on a patient with terminal deletion of the long arm of chromosome 14 displaying brain interhemispheric fusion limited to the midline anterior frontal cortex associated with hypoplastic corpus callosum and incomplete rotation of the left hippocampus in a clinical setting of motor and intellectual disability with poor language, and social behavior abnormalities with aggressiveness. Some possible correlations between clinical signs and symptoms and various aspects of the complex brain malformation are briefly discussed and compared with other known abnormalities of chromosome 14. The different neuropathology of the most common forms and the new forms of holoprosencephaly recently described is also discussed and leads us to suggest classifying the interhemispheric fusion of this case as a \u80\u9cminimal\u80\u9d form of holoprosencephaly. This appears to be the first description in a 14q deletion patient

Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy

ObjectiveTo determine if a significant proportion of patients with myoclonic-astatic epilepsy (MAE) have glucose transporter 1 (GLUT1) deficiency.DesignGenetic analysis.SettingAmbulatory and hospitalized care.PatientsEighty-four unrelated probands with MAE were phenotyped andSLC2A1was sequenced and analyzed by multiplex ligation-dependent probe amplification. Any identified mutations were then screened in controls.Main Outcome MeasureAnySLC2A1mutations.ResultsFour of 84 probands with MAE had a mutation ofSLC2A1on sequencing. Multiplex ligation-dependent probe amplification analysis did not reveal any genomic rearrangements in 75 of the remaining cases; 5 could not be tested. Two patients with MAE withSLC2A1mutations also developed paroxysmal exertional dyskinesia in childhood.ConclusionsFive percent of our patients with MAE hadSLC2A1mutations, suggesting that patients with MAE should be tested for GLUT1 deficiency. Diagnosis of GLUT1 deficiency is a strong indication for early use of the ketogenic diet, which may substantially improve outcome of this severe disorder