Advices for Life


December 20, 2016 00:04

Mitochondrial diseases caused by disturbance of beta oxidation of fatty acids

study of mitochondrial disease caused by a violation of beta oxidation of fatty acids with different carbon chain length was started in 1976, when scientists first described in patients with deficiency of acyl-CoA dehydrogenase, medium chain fatty acids and glutaric acidemia type II.Currently, this group of diseases includes no less than 12 separate clinical entities, whose origin is associated with genetically determined disorders of the transmembrane transport of fatty acids (systemic carnitine deficiency, deficiency of carnitine I and II, the acylcarnitine-karnitintranslokazy) and subsequent mitochondrial beta-oxidation (acyl deficit-CoA and 3-hydroxy-acyl-CoA dehydrogenases fatty acids of varying carbon chain length, glutaric acidemia type II).Frequency deficit acyl-CoA dehydrogenase, medium chain fatty acids is 1: 8900 newborns, the incidence of other forms of pathology is not yet established.

genetic data and pathogenesis.Diseases are autosomal recessive inheritance.

Pathogenesis of fatty acid

metabolism diseases associated with the depletion of carbohydrate reserves in conditions of metabolic stress (intercurrent infectious diseases, physical or emotional overload, fasting, surgery).In this situation, the lipids are necessary to replenish the source of energy the body needs.The activation of defective transport processes and fatty acid beta-oxidation.From the mobilization of omega-oxidation are accumulated in biological fluids dicarboxylic acids, their toxic derivatives of carnitine conjugates - resulting secondary Carnitine deficiency develops.

symptoms.Clinical manifestations of fatty acid metabolism diseases are very similar.Disease is usually characterized by paroxysmal current.There are heavy (early, generalized) and light (later, muscle) form, characterized by varying degrees of enzyme deficiency or tissue localization.

severe form manifests early in life, including in the neonatal period.The main symptoms: vomiting, generalized tonic-clonic seizures and infantile spasms, progressive lethargy, drowsiness, hypotonia, impairment of consciousness up to coma, cardiac disorder (rhythm disturbance or cardiomyopathy), enlargement of the liver (Reye's syndrome).The disease is accompanied by mortality (20%) and the risk of sudden infant death.

Easy form usually appears for the first time in school age and adolescents.Develop muscle pain, weakness, fatigue and motor awkwardness, dark color urine (myoglobinuria).

additional characteristic clinical signs of deficiency of 3-hydroxy-acyl-Co A Dehydrogenase fatty acids with a long carbon chain - peripheral neuropathy and retinitis pigmentosa.Do mothers whose children are likely to have this enzyme defect, often complicated by pregnancy - developed fatty liver, thrombocytopenia, increased activity of transaminases.

These laboratory studies.Biochemical disorders include: gipoketoticheskuyu hypoglycemia, metabolic acidosis, increase of blood lactic acid, ammonia, elevated transaminase and creatine, low levels of total carnitine content increases its esterified form.The urine usually show a high excretion of dicarboxylic acids with a carbon chain length corresponding to their hydroxylated derivatives and acyl carnitines.

Differential diagnosis is required to carry out with mitochondrial encephalomyopathies, organic acidemia, cardiomyopathies of different origin, different types of epilepsy, atsetonemicheskoy vomiting.

treatment.The main method of treatment of diseases of transport and oxidation of fatty acids - nutritional therapy.It is based on two principles: the elimination of starvation (shortening intervals between meals) and enrichment of dietary carbohydrates with a sharp restriction of receiving lipids.Additionally, for the treatment of pathologies associated with defective or transport of fatty acid oxidation with a long carbon chain, it is recommended the use of special mixtures of medium chain triglycerides (contraindicated in defect-acyl-CoA dehydrogenases fatty acids with medium and short chain).

used for medical correction levocarnitine (50-100 mg / kg body weight per day depending on the age and weight of the patients), glycine (100-300 mg / day), riboflavin (20 to 100 mg / day).During metabolic crisis shown intravenous administration of 10% glucose solution at the rate of 7-10 mg / kg per minute under the control of its level in blood.Glucose administration not only compensates fabric deficiency, but also inhibits lipolysis and lowers production toxic derivatives of fatty acids.