Which are the causes of Systemic Primary Carnitine Deficiency?

Systemic Primary Carnitine Deficiency (SPCD) is a rare genetic disorder that affects the body's ability to transport long-chain fatty acids into the mitochondria, where they are used as a source of energy. This condition is caused by mutations in the SLC22A5 gene, which encodes a protein called carnitine transporter OCTN2.

1. Genetic Mutations: The primary cause of SPCD is the presence of mutations in the SLC22A5 gene. These mutations can be inherited from one or both parents, leading to a deficiency in the production or function of the OCTN2 protein. Without functional OCTN2, the body is unable to effectively transport carnitine into cells, resulting in a buildup of fatty acids and a deficiency of carnitine in the bloodstream.

2. Inherited Autosomal Recessive Disorder: SPCD follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder. If both parents are carriers of the mutated gene, each child has a 25% chance of inheriting two copies and developing SPCD.

3. Reduced Carnitine Levels: Carnitine is an essential molecule required for the transport of fatty acids into the mitochondria. In SPCD, the impaired function of the OCTN2 protein leads to reduced levels of carnitine in the body. This deficiency disrupts the normal metabolism of fatty acids, preventing their efficient utilization as an energy source.

4. Symptoms and Manifestations: The deficiency of carnitine in SPCD affects various organs and systems in the body. Common symptoms include muscle weakness, low blood sugar (hypoglycemia), cardiomyopathy (weakening of the heart muscle), liver dysfunction, and developmental delays in infants. These symptoms can vary in severity and may present at different ages.

5. Diagnosis and Treatment: SPCD is typically diagnosed through genetic testing to identify mutations in the SLC22A5 gene. Additionally, blood tests can measure carnitine levels and confirm the deficiency. Treatment involves lifelong carnitine supplementation to restore normal carnitine levels and improve energy metabolism. Early diagnosis and prompt treatment are crucial in managing the symptoms and preventing complications associated with SPCD.

In conclusion, Systemic Primary Carnitine Deficiency is primarily caused by genetic mutations in the SLC22A5 gene, leading to a deficiency in the carnitine transporter protein OCTN2. This autosomal recessive disorder results in reduced carnitine levels, affecting energy metabolism and leading to various symptoms. Timely diagnosis and lifelong carnitine supplementation are essential for managing this rare genetic disorder.