multiple acyl-CoA dehydrogenase deficiency

Multiple acyl-CoA dehydrogenase deficiency is a metabolic disorder that impairs the oxidation of fatty acids and amino acids, leading to energy production deficiencies. It is caused by mutations in the ETFA, ETFB, or ETFDH genes, which play key roles in electron transfer during metabolism. The condition exhibits a wide clinical spectrum, with some affected individuals presenting as neonates with severe metabolic acidosis, cardiomyopathy, and liver disease, and others developing milder, episodic symptoms later in childhood or adulthood. This disorder is rare, affecting roughly 1 to 9 people per million.

The clinical presentation of multiple acyl-CoA dehydrogenase deficiency is variable. A characteristic feature seen in all affected individuals is glutaric aciduria. Many patients may also experience exercise intolerance and intermittent diarrhea, while subsets show elevated urine levels of suberic acid, 3-methyladipic acid, as well as episodes of pancreatitis and methylmalonic aciduria. Not all individuals experience all these features, and severity varies considerably.

This condition is caused by pathogenic variants in the ETFA, ETFB, or ETFDH genes, which encode proteins essential for proper electron transfer in fatty acid and amino acid oxidation. It is inherited in an autosomal recessive manner, meaning that a person must inherit a mutated copy from each parent to be affected. Multiple acyl-CoA dehydrogenase deficiency is more common when parents share a common ancestor, as the probability of both carrying a rare variant increases. Families are encouraged to seek genetic counseling to understand the implications for family planning.

Currently, management of multiple acyl-CoA dehydrogenase deficiency focuses on supportive care and symptom control because no treatments have been specifically approved for this condition. Care is highly individualized and typically involves a multidisciplinary team addressing metabolic crises, nutritional support, and management of muscle weakness or respiratory difficulties. Ongoing surveillance is an essential part of long-term care to identify and manage emerging complications. Genetic counseling is also recommended to help patients and families navigate treatment options and family planning decisions.

Outcomes in multiple acyl-CoA dehydrogenase deficiency vary widely, with some individuals showing severe symptoms in infancy and others experiencing milder, episodic issues later in life. With current treatments, many affected individuals live into adulthood, with life expectancy ranging broadly from early childhood to several decades. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to work with metabolic specialists and genetic counselors for ongoing guidance, and connecting with support groups can offer additional help. Advances in modern care continue to improve the quality of life for many living with this condition.

Several clinical trials are currently investigating new treatment approaches for multiple acyl-CoA dehydrogenase deficiency. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their healthcare team about eligibility.