carnitine-acylcarnitine translocase deficiency

Carnitine-acylcarnitine translocase deficiency is a life-threatening disorder of fatty acid oxidation that primarily affects the neonatal period. It is caused by pathogenic variants in the SLC25A20 gene, which encodes a protein essential for the transport of carnitine and acylcarnitine across the mitochondrial membrane. Affected newborns typically present with severe hypoglycemia, cardiac arrhythmias, and hepatic dysfunction. This condition is very rare, affecting fewer than 1 in one million individuals.

The clinical presentation is severe and multi-system in nature. In the neonatal period, there is a high likelihood of hypoglycemia, often accompanied by life-threatening events such as cardiac arrest and arrhythmias, including ventricular tachycardia and cardiomyopathy. Liver involvement is evident with hepatic steatosis, elevated hepatic transaminase levels, and hepatomegaly, while muscle involvement includes muscle weakness, rhabdomyolysis, and elevated creatine kinase after exercise. Neurologically, affected infants frequently exhibit encephalopathy, irritability, and global developmental delay. Not all individuals experience all features, and severity varies considerably.

Carnitine-acylcarnitine translocase deficiency is caused by pathogenic variants in the SLC25A20 gene, which encodes a protein that plays a critical role in mitochondrial fatty acid oxidation. The disorder is inherited in an autosomal recessive pattern, meaning that an affected individual has received one altered copy of the gene from each parent. This inheritance pattern also implies an increased risk when parents share a common ancestor, as they are more likely to carry the same rare variant. Genetic counseling is recommended for families to discuss recurrence risks and options for family planning.

Currently, management focuses on supportive care and symptom management since there are no FDA-approved treatments specifically for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include metabolic specialists, cardiologists, neurologists, and critical care experts. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. In addition, genetic counseling is recommended to help families understand the condition and discuss available supportive strategies.

Outcomes for individuals with carnitine-acylcarnitine translocase deficiency vary considerably. Many affected infants experience life-threatening complications in the neonatal period, while others may reach a relatively stabilized phase with ongoing supportive care. With current standards of care, improvements in management have led to better survival and quality of life for some individuals, though variability in outcomes remains high. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with metabolic specialists and genetic counselors for personalized guidance.

Several clinical trials are currently exploring new treatment approaches for carnitine-acylcarnitine translocase deficiency. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.