RESUMEN
BACKGROUND: Secondary lactate acidosis is found in children with hypoxaemia, with impaired tissue perfusion, in hepatic and renal failure or in intoxications. Primary lactate acidosis is usually caused by hereditary metabolic disorders. The objective of the trial was to analyze the causes which lead in childhood to the development of primary hyperlactacidaemia. METHODS AND RESULTS: The authors examined during 1995-1996 the lactate and pyruvate concentration in 479 children referred by paediatric and neurological departments with a suspect hereditary metabolic disturbances. A raised lactate in blood or cerebrospinal fluid > 2.3 mmol/l was found in 230 children incl. 49 where a metabolic disorder was detected. Ten children had impaired cytochrome c oxidase, two children had a combined deficience of NADH dehydrogenase and cytochrome c oxidase, three children had a deficience of the pyruvate dehydrogenase (PDH) complex, one child had a deficience of ATP synthase and seven children suffered from impaired beta-oxidation. Glycogenosis type I, III or IX was found in 13 children. In three children organic aciduria was found, two children had an impaired urea cycle and three children impaired fructose metabolism. In five children a low level of free and total carnitene was found as a result of valproate treatment. A significant increase of the lactate level by more than 1 mmol/l during an oral glucose load was found in 11 of 16 children with impairment of the respiratory chain or PDH complex. In 58 children concurrently lactate in blood and cerebrospinal fluid assessed but no correlation of lactate levels was found. CONCLUSIONS: In patients with suspect hereditary metabolic disorders examination of lactate, pyruvate and alanine levels can be considered a screening test for detection of mitochondrial disorders. It remains difficult to reveal the cause of hyperlactacidaemia in a sick child even if a wide range of laboratory methods are used which contribute to the diagnosis of hereditary metabolic disorders.
Asunto(s)
Acidosis Láctica/etiología , Acidosis Láctica/diagnóstico , Acidosis Láctica/metabolismo , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién NacidoRESUMEN
BACKGROUND: A heteroplasmic A3243G point mutation in tRNALeu(UUR) gene of mitochondrial DNA (mtDNA) is found in patients with MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes), less frequently in patients with other dominating clinical features, such as deafness, diabetes mellitus type 2, hypertrophic cardiomyopathy, renal problems or inborn development defects. Present report describes histochemical, enzymatic and molecular biology studies of the family with clinical variant of meals syndrome. METHODS AND RESULTS: A 45-year-old woman with progressive muscle weakness, external ophtalmoplegia, perceptive deafness, ischemic heart disease, diabetes mellitus type 2 and hyperlactacidemia was metabolically investigated because the multiorgan problems indicated mitochondrial origin of the disease. Muscle biopsy revealed pronounced myopathic changes, ragged red fibers and decreased activity of respiratory chain enzymes - succinate cytochrome c reductase (< 5% control) and cytochrome c oxidase (< 10% control). Restriction fragment analysis of mtDNA from muscle, blood and hair follicles detected heteroplasmic A -> G mutation in the position 3243 of the tRNALeu(UUR) gene, which was more pronounced in muscle (28% of total mtDNA) than in blood (12%) or in hair follicles (10%). No mutation was found in blood and hair follicles of patient's mother and daughter. CONCLUSIONS: Diagnostics of mitochondrial diseases require close collaboration of clinicians with specialised laboratories. Treatment of mitochondrial disorders is only symptomatic, however, early diagnosis of the molecular defect is important for genetic counselling.