Carnitine deficiency or dysfunction in its transport and metabolism can lead to a variety of diseases. These conditions may be primary (genetic) or secondary (acquired), and they affect energy metabolism, particularly in tissues with high fatty acid oxidation requirements such as skeletal muscle, heart, and liver.
| Disease / Condition | Role of Carnitine in Pathogenesis | Notes / Evidence |
| Primary Systemic Carnitine Deficiency | Mutation in SLC22A5 gene encoding OCTN2 transporter leads to defective carnitine uptake, causing reduced intracellular carnitine. | Presents with hypoketotic hypoglycemia, skeletal muscle weakness, cardiomyopathy; treated with oral L-carnitine. |
| Secondary Carnitine Deficiency | Due to increased carnitine loss (hemodialysis, organic acidemias, certain drugs) or reduced synthesis. | Symptoms include fatigue, muscle weakness, metabolic decompensation during stress. |
| Organic Acidemias (e.g., Propionic Acidemia, Methylmalonic Acidemia) | Accumulated organic acids conjugate with carnitine, depleting free carnitine levels. | Supplementation with L-carnitine aids in removal of toxic acyl groups. |
| Fatty Acid Oxidation Disorders (e.g., MCAD, VLCAD deficiencies) | Defective β-oxidation increases reliance on carnitine for buffering excess acyl groups. | Carnitine supplementation may help in certain defects, though use depends on specific disorder. |
| Hemodialysis-Related Carnitine Loss | Dialysis removes free and acylcarnitine, leading to deficiency over time. | Can cause intradialytic hypotension, muscle cramps, fatigue; L-carnitine can be given IV post-dialysis. |
| Valproic Acid-Induced Carnitine Deficiency | Valproate conjugates with carnitine, increasing urinary loss and impairing fatty acid oxidation. | Supplementation prevents hepatotoxicity and hyperammonemia. |
| Cardiomyopathy Related to Carnitine Deficiency | Low carnitine impairs cardiac energy metabolism, reducing contractile function. | Reversible with supplementation in primary deficiency. |
| Myopathy Due to Carnitine Deficiency | Reduced muscle carnitine impairs endurance and muscle strength. | Can occur in both genetic and acquired deficiencies. |