carnitine palmitoyl transferase 1A deficiency

Carnitine palmitoyl transferase 1A deficiency is an inborn error of metabolism that primarily affects the liver and kidneys by impairing mitochondrial oxidation of long chain fatty acids. The condition arises from pathogenic variants in the CPT1A gene, which disrupts the normal energy production during fasting. It is an autosomal recessive disorder that typically presents in infancy or early childhood when fasting-induced metabolic stress occurs. Being very rare, this condition is understood to affect fewer than 1 in 1,000,000 people.

Individuals with this condition commonly experience fasting-induced hypoglycemia that is accompanied by low levels of ketones (hypoketotic hypoglycemia) and a characteristic pattern of metabolic disturbances including dicarboxylic aciduria. Almost invariably, affected children present with gastrointestinal symptoms such as diarrhea and feeding difficulties, as well as neurologic features including recurrent encephalopathy, motor delay, and hyporeflexia. Other findings such as elevated liver enzymes, hypotonia, seizures, atypical behavior, and reduced tendon reflexes are also frequently reported. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the CPT1A gene, which encodes an enzyme essential for the mitochondrial oxidation of long chain fatty acids. The deficiency reduces the liver’s ability to convert fatty acids into energy during fasting, leading to metabolic crises and liver dysfunction. It is inherited in an autosomal recessive pattern, meaning that affected children inherit one altered copy of the gene from each parent. Because the condition is more likely when both parents share common ancestry, carrier testing may be especially relevant for families with shared heritage.

Currently, management focuses on supportive care and symptom management since there are no FDA-approved or specifically foundational therapies for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address both metabolic and neurologic challenges. Supportive care may include nutritional management to avoid prolonged fasting, careful metabolic monitoring to prevent crises, and regular surveillance to detect potential complications such as liver dysfunction. In addition, genetic counseling is recommended to help families understand the condition and its implications for future family planning.

The course of carnitine palmitoyl transferase 1A deficiency is highly variable, with outcomes depending on the severity of metabolic decompensations and the timeliness of supportive interventions. With current standards of care, many individuals experience stabilization after the initial metabolic crises, although they remain at risk for recurrent episodes and complications such as liver dysfunction. Outcomes described in medical literature continue to evolve as standards of care improve, and individual prognoses differ based on access to specialized management and prompt intervention during metabolic stress. Families often find it helpful to connect with metabolic specialists and genetic counselors for ongoing guidance and support.

Several clinical trials are currently underway exploring new treatment approaches for carnitine palmitoyl transferase 1A deficiency. Individuals interested in learning more about ongoing research may wish to search ClinicalTrials.gov or consult their care team to identify potential trial opportunities.