Early onset Alexander disease: a case report with evidence for manifestation of the disorder in neurohypophyseal pituicytes.

We report the first case of Alexander disease diagnosed and published in the region of former Czechoslovakia. The case was characterized by early (late infantile) onset, the absence of megacephaly but with extensive internal hydrocephaly, despite a patent aqueduct. Neuropathology revealed severe depletion ofoligodendroglia and myelin, loss of axons, prominent astrocytosis with massive intracellular, dense globular GFAP aggregates which differed from typical Rosenthal fibers.

Deficiency of mitochondrial ATP synthase of nuclear genetic origin.

We present clinical and laboratory data from 14 cases with an isolated deficiency of the mitochondrial ATP synthase (7-30% of control) caused by nuclear genetic defects. A quantitative decrease of the ATP synthase complex was documented by Blue-Native electrophoresis and Western blotting and was supported by the diminished activity of oligomycin/aurovertin-sensitive ATP hydrolysis in fibroblasts (10 cases), muscle (6 of 7 cases), and liver (one case). All patients had neonatal onset and elevated plasma lactate levels.

Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family.

Inheritance and expression of mitochondrial DNA (mtDNA) mutations are crucial for the pathogenesis of Leber hereditary optic neuropathy (LHON). We have investigated the segregation and functional consequences of G3460A mtDNA mutation in 27 members of a three-generation family with LHON syndrome. Specific activity of respiratory chain complex I in platelets was reduced in average to 56%, but no direct correlation between the mutation load and its biochemical expression was found.

Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome.

Subacute necrotising encephalomyopathy (Leigh syndrome) due to cytochrome c oxidase (COX) deficiency is often caused by mutations in the SURF1 gene, encoding the Surf1 protein essential for COX assembly. We have investigated five patients with different SURF1 mutations resulting in the absence of Surf1 protein. All of them presented with severe and generalised COX defect.

[A new missense mutation of 574C>T in the SURF1 gene--biochemical and molecular genetic study in seven children with Leigh syndrome].

Background: Leigh disease, subacute necrotizing encephalopathy, is a serious mitochondrial disorder of energy-providing metabolism. Clinical presentation usually starts in infancy as a progressive neurodegenerative disorder with retardation and regression of psychomotor development. The most common form of the disease is associated with deficiency of the cytochrome c oxidase (COX) due to SURF1 gene mutations.