Question

Why would there be steatosis (lipid accumulation) in the liver of a patient with Systemic Carnitine deficiency? Why will skeletal muscle carnitine content remain below normal despite high-dose carnitine therapy in this patient?

Answer 1

Lipid accumulation or steatosis may be observed in a patient with systemic primary carnitine deficiency because of the inefficient mechanism of lipid metabolism. This means that the lipids are not metabolized and fatty acid metabolism disorders are often found in these patients. These leads to the accumulation of lipid in the hepatocytes (liver cells) and lipid storage myopathy. The vascular endothelial cells show abnormal lipid deposits.

Carnitine is a quaternary amine. It plays an important role in the regulation of the substrate flux. It is an important co-factor for the mechanism where the fatty-acid chains are converted to acylcarnitine derivatives and may be transferred to mitochondria with the help of beta-oxidation. As mentioned above, the fatty acid metabolism is impaired in these patients. So, the Carnitine is not metabolized to form acylcarnitine derivatives.

The fatty acid oxidation is impaired and this hinders the transportation of carnitine to the muscle tissue. Therefore, even after providing high-dose carnitine therapy, the carnitine cannot be transported to muscles tissue and hence, the carnitine content remains low.