Disease relevance of Diffuse Cerebral Sclerosis of Schilder

• Defects of mitochondrial polymerase gamma (POLG) underlie neurological diseases ranging from myopathies to parkinsonism and infantile Alpers syndrome [1].
• The A467T mutation is associated with a wide range of mitochondrial disorders, including Alpers syndrome, juvenile spinocerebellar ataxia-epilepsy syndrome, and progressive external ophthalmoplegia, each with vastly different clinical presentations, tissue specificities, and ages of onset [2].
• Increased signal intensity from lactate occurred in patients with Leigh disease, neuroaxonal dystrophy, Schilder disease, and Cockayne disease, which indicated a disturbed energy metabolism in the examined region [3].
• The term "Schilder's disease" has been used to describe conditions as disparate as adrenoleukodystrophy, myelinoclastic diffuse sclerosis, and postinfectious and postvaccinal encephalomyelitis [4].
• Valproate-induced liver failure in one of two siblings with Alpers disease [5].

High impact information on Diffuse Cerebral Sclerosis of Schilder

• In two unrelated pedigrees of Alpers' syndrome, each affected child was found to carry a homozygous mutation in exon 17 of the POLG locus that led to a Glu873Stop mutation just upstream of the polymerase domain of the protein [6].
• Computed tomograms (CT) demonstrated symmetrical low-density lesions in the white matter of the posterior portion of the cerebral hemispheres in a 9-year-old boy with adrenoleukodystrophy (Schilder's disease) [7].
• The findings, taken together with those of previously reported cases, suggest that Baló's concentric sclerosis is a variant of MS, and the concentric lesion may be an intermediary form in evolution of a chronic active MS plaque [8].
• We report 2 siblings with Alpers disease who were discordant for exposure to valproate (VPA) [5].
• We will present 8 children with progressive infantile or juvenile poliodystrophy (Alpers' disease), associated with a defect in pyruvate metabolism [9].

Chemical compound and disease context of Diffuse Cerebral Sclerosis of Schilder

• Progressive infantile poliodystrophy (Alpers' disease) with a defect in citric acid cycle activity in liver and fibroblasts [10].
• Letter: Schilder's disease: cholesterol metabolism in cultured fibroblasts [11].

Biological context of Diffuse Cerebral Sclerosis of Schilder

• Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome [12].
• Most patients with Alpers syndrome have been found to be compound heterozygotes, carrying two pathogenic mutations in trans at the POLG locus [12].

Gene context of Diffuse Cerebral Sclerosis of Schilder

• POLG mutations and Alpers syndrome [13].
• The POLG1 mutations can cause juvenile and childhood Alpers disease [14].

References