Very long chain fatty acids

Very long chain fatty acids (VLCFA) have a chain length of at least 22 carbon atoms. VLCFA are both supplied with food and synthesized in the body. Very long chain fatty acids are synthesized in the endoplasmic reticulum and degraded by beta-oxidation in peroxisomes. Representatives of the very long-chain fatty acids found in humans are docosanoic acid, tetracosanoic acid and hexacosanoic acid. The highest concentrations of saturated VLCFA are found in myelin and in the erythrocyte membrane. Here they make up 1-5 % of the total fatty acids. The proportion of VLCFA in fatty acids of plasma and adrenal cortex is much lower (0.01 %).

Very long-chain fatty acids (VLCFAs) play an important role in membrane structure and cellular signaling. Fatty acid elongases catalyze the first and rate-limiting step of VLCFA synthesis. Heterozygous mutations in ELOVL4, the gene encoding one of the elongases, cause macular degeneration in humans (and retinal abnormalities in mice).

The determination of VLCFAs is used to diagnose peroxisomal diseases such as beta-oxidation disorders or disorders of oxisome formation (e.g. adrenoleukodystrophy, Zellweger syndrome).

In tissues of patients with adrenoleukodystrophy, the concentrations of VLCFA are increased. A two- to threefold increase in the saturated fatty acids C24:0 and C26:0 is found in plasma, erythrocytes and fibroblasts. The proportion of VLCFA in the cholesterol esters of brain tissue is significantly increased by a factor of four to ten in ALD patients and is particularly evident in the zones of active demyelination, while intact areas of white brain matter are hardly affected.

VLCAD deficiency is a clinically heterogeneous disease with 3 main phenotypes. It is caused by mutations in the VLCAD gene(ACADVL; 17p13.1). Severe infantile VLCAD deficiency begins early, usually in the first 3-12 months of life, but also in the neonatal period. Common causes of high mortality are hypoketotic hypoglycemia, liver dysfunction, cardiac arrhythmias and cardiomyopathy. Pericardial effusions have also been described. Moderate infantile/childhood VLCAD deficiency begins later (from the early neonatal period to early childhood) and manifests with hypoketotic hypoglycemia. Cardiomyopathy is rare and mortality is lower. Late myopathic VLCAD deficiency manifests in older children (usually > 10 years) and young adults with isolated muscle involvement (exercise intolerance, myalgia, rhabdomyolysis, myoglobinuria). Triggers are physical exertion, fasting, cold/heat and/or stress. Viral infections can also trigger or exacerbate these symptoms. Renal failure is a rare complication leading to death. Some patients with the myopathic form had hypoglycemia in infancy or childhood.