From the FDA Drug Label
Primary systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0. 4 or abnormally elevated concentrations of acylcarnitine in the urine.
The enzyme deficient in primary systemic carnitine deficiency is not directly specified in the label. However, the label mentions that carnitine plays a crucial role in facilitating long-chain fatty acid entry into cellular mitochondria.
- Low acylcarnitine levels may be associated with carnitine deficiency.
- The label does mention medium chain fatty acylCoA dehydrogenase deficiency as a condition that can lead to secondary carnitine deficiency 1. However, it does not directly link low acylcarnitine levels to a specific enzyme deficiency.
From the Research
Low acylcarnitine levels are most likely indicative of a deficiency in carnitine-acylcarnitine translocase (CACT) enzyme, as this enzyme plays a crucial role in the transport of acylcarnitines across the inner mitochondrial membrane. This enzyme is essential for the proper functioning of the carnitine cycle, which is responsible for the transport of long-chain fatty acids into mitochondria for beta-oxidation and energy production. When CACT is deficient, the body cannot properly transport acylcarnitines into the mitochondria, resulting in decreased acylcarnitine levels in blood tests 2. CACT deficiency is a rare inherited metabolic disorder that affects the body's ability to use certain fats for energy, particularly during periods of fasting or illness. Patients with this condition may experience symptoms such as hypoglycemia, lethargy, seizures, and liver dysfunction, especially during times of metabolic stress. Management typically involves avoiding prolonged fasting, following a diet low in long-chain fatty acids, and supplementing with medium-chain triglycerides which can bypass the CPT system. Early diagnosis and proper management are essential to prevent metabolic crises and associated complications.
Some key points to consider in the management of CACT deficiency include:
- Avoiding prolonged fasting and ensuring adequate glucose intake to prevent hypoglycemia 2
- Following a diet low in long-chain fatty acids to reduce the burden on the mitochondrial fatty acid oxidation pathway 3
- Supplementing with medium-chain triglycerides to provide an alternative source of energy 3
- Monitoring for cardiac involvement, including arrhythmias and cardiomyopathy, which are common complications of CACT deficiency 2
- Considering adjunctive therapies, such as anaplerosis with d,l-3-hydroxybutyrate or Triheptanoin, to improve metabolic stability and reduce the risk of complications 2
Overall, the management of CACT deficiency requires a comprehensive approach that takes into account the patient's nutritional, metabolic, and cardiac needs. By prioritizing early diagnosis and proper management, it is possible to improve outcomes and reduce the risk of complications in patients with this rare but potentially debilitating disorder.