DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis.

BACKGROUND: Leucoencephalopathy with brain stem and spinal cord involvement and high brain lactate (LBSL) was first defined by characteristic magnetic resonance imaging and spectroscopic findings. The clinical features include childhood or juvenile onset slowly progressive ataxia, spasticity, and dorsal column dysfunction, occasionally accompanied by learning difficulties. Mutations in DARS2, encoding mitochondrial aspartyl-tRNA synthetase, were recently shown to cause LBSL. The signs and symptoms show some overlap with the most common leucoencephalopathy of young adults, multiple sclerosis (MS). OBJECTIVE: To clarify the molecular background of LBSL patients in Finland, and to look for DARS2 mutations in a group of MS patients. METHODS: Clinical evaluation of LBSL patients, DARS2 sequencing and haplotype analysis, and carrier frequency determination in Finland. RESULTS: All eight LBSL patients were compound heterozygotes for DARS2 mutations: all carried R76SfsX5 change, seven had M134_K165del, and one had C152F change. Axonal neuropathy was found in five of the eight patients. The carrier frequencies of the R76SfsX5 and M134_K165del mutations were 1:95 and 1:380, respectively. All patients shared common European haplotypes, suggestive of common European LBSL ancestors. No enrichment of the two common DARS2 mutations was found in 321 MS patients. CONCLUSION: All LBSL patients were compound heterozygotes, which suggests that DARS2 mutation homozygosity may be lethal or manifest as a different phenotype. The authors show here that despite identical mutations the clinical picture was quite variable in the patients. Axonal neuropathy was an important feature of LBSL. DARS2 mutations cause childhood-to-adolescence onset leucoencephalopathy, but they do not seem to be associated with MS.

Serum cholesterol increase in a middle-aged male industrial population during ten years (1976-1986) and general food consumption changes in Czechoslovakia.

The authors evaluate the coronary risk factor changes in middle-aged men from the point of view of changed nutritional habits of the whole population (yearly per capita consumption of different food). They compared 3,754 men aged 40-50 years when screened in 1976-77 (Skoda I Study) and 568 men aged 40-50 years when screened in 1986-88 (Skoda II Study). During the 10-year period, a significant decrease of smoking habits was observed, hypertension prevalence remained unchanged and hypercholesterolaemia prevalence increased significantly. The estimated yearly per capita consumption of meat and fat remained unchanged in the years 1975-1985, however, the structure of consumption revealed a gradual change towards food containing high amounts of animal fat. Education efforts during the 10-year period (1976-1986) led to a decrease in smoking habits in middle-aged men leaving hypertension control unchanged. The observed increase of cholesterol levels may be attributed to inappropriate nutritional habits gradually worsening in the whole population probably due to a socio-economic depression.