Leber's hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients.

Background: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. Here we describe the clinical and molecular characteristics of 20 patients with disease onset after the age of 50 years (late onset-LHON).

Methods: From a cohort of 251 affected and 277 unaffected LHON carriers, we identified 20 patients with onset of visual loss after the age of 50 years.

Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation.

Ninety-five percent of Leber hereditary optic neuropathy (LHON) patients carry a mutation in one out of three mtDNA-encoded ND subunits of complex I. Penetrance is reduced and more male than female carriers are affected. To assess if a consistent biochemical phenotype is associated with LHON expression, complex I- and complex II-dependent adenosine triphosphate synthesis rates (CI-ATP, CII-ATP) were determined in digitonin-permeabilized peripheral blood mononuclear cells (PBMCs) of thirteen healthy controls and for each primary mutation of a minimum of three unrelated patients and of three unrelated carriers with normal vision and were normalized per mitochondrion (citrate synthase activity) or per cell (protein content).

Gene-environment interactions in Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought to precipitate the visual failure and explain the marked incomplete penetrance of LHON, but previous small studies have failed to confirm this to be the case. LHON has no treatment, so identifying environmental triggers is the key to disease prevention, whilst potentially revealing new mechanisms amenable to therapeutic manipulation.

Quality of life in patients with leber hereditary optic neuropathy.

Purpose: Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial optic neuropathy characterized by bilateral, severe loss of central vision. In this study, the first formal assessment was conducted of visual disability in affected and unaffected individuals from molecularly confirmed LHON pedigrees.

Methods: Four hundred two LHON carriers--196 affected and 206 unaffected--from 125 genealogically distinct pedigrees were prospectively interviewed using the well-validated visual function index (VF-14) questionnaire: m.

Postnatal onset cortical dysplasia associated with infarction of white matter.

On MRI at 35 weeks of a boy born at 25 weeks, focal disorganization of the cortex was observed near a frontal venous infarct developed in the first week. Disruption of the final steps of cell migration, injury to the subplate and/or disruption of corticospinal axons are possible mechanisms behind it. Preterms with white matter lesions at or below 25 weeks postconceptional age should be scrutinized for cortical dysplasia.

Sonographic maturation of third-trimester cerebellar foliation after birth.

The development of cerebellar folia of third-trimester preterms has not been described with ultrasound before. We set out to determine normal development of the pons and cerebellar folia for future measurements of hypoplasia and atrophy. Study sonograms were made in preterms admitted to the neonatal intensive care unit with postmenstrual age (PMA) from 25 wk until term.