From the Guidelines
Hereditary metabolic diseases associated with low carnitine levels include primary carnitine deficiency, carnitine uptake defect, carnitine palmitoyltransferase I and II deficiencies, and very long-chain acyl-CoA dehydrogenase deficiency, among others. These diseases are characterized by impaired fatty acid oxidation, leading to low carnitine levels 1. The specific diseases associated with low carnitine levels are:
- Carnitine uptake defect
- Carnitine palmitoyltransferase I (CPTI) deficiency
- Carnitine palmitoyltransferase II (CPTII) deficiency
- Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
- Long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
- Trifunctional protein (TFP) deficiency
- Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
- Medium/short-chain L-3-hydroxyacyl-CoA (M/SCHAD) dehydrogenase deficiency
- Medium-chain 3-ketoacyl-CoA thiolase (MCKAT) deficiency
- Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
- Multiple-CoA dehydrogenase (MAD) deficiency (-ETF,-ETF, ETF-QO deficiency) (Glutaric acidemia type II)
- Dienoyl-CoA reductase deficiency
These diseases can lead to severe health consequences, including hypoglycemia, cardiomyopathy, muscle weakness, and even sudden death, particularly during fasting or illness when fat metabolism is crucial for energy production 1. L-carnitine supplementation is essential for managing these diseases, with typical doses ranging from 50-400 mg/kg/day divided into 2-3 doses. Carnitine is essential for transporting long-chain fatty acids into mitochondria for energy production, and deficiency can disrupt this process, leading to the aforementioned health consequences 1.
From the FDA Drug Label
Primary systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues Secondary carnitine deficiency can be a consequence of inborn errors of metabolism Conditions for which this effect has been demonstrated are: glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency
The hereditary metabolic diseases associated with low carnitine levels are:
- Primary systemic carnitine deficiency
- Glutaric aciduria II
- Methyl malonic aciduria
- Propionic acidemia
- Medium chain fatty acylCoA dehydrogenase deficiency 2
From the Research
Hereditary Metabolic Diseases Associated with Low Carnitine Levels
The following hereditary metabolic diseases are associated with low carnitine levels:
- Primary myopathic carnitine deficiency, characterized by low carnitine concentrations usually restricted to muscle 3
- Systemic carnitine deficiency, which shows decreased concentrations in other organs and plasma as well 3
- Medium-chain acyl-CoA dehydrogenase deficiency, a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting 4, 5, 6
- Organic acidurias, which exhibit an increased excretion of carnitine esters and an insufficiency of free carnitine 3
- Other defects in beta-oxidation, Krebs cycle or respiratory chain enzymes, which may be associated with secondary carnitine deficiency 3
- LCAD, SCAD, and HMG-CoA lyase deficiencies, two forms each of CPT and MAD deficiencies, and an incompletely characterized disorder of primary carnitine deficiency, all of which are inherited diseases in the pathway of mitochondrial fatty acid oxidation 7
Characteristics of These Diseases
These diseases often present with:
- Episodes of coma and hypoglycemia induced by fasting 4, 7
- Hypertrophic cardiomyopathy and chronic skeletal muscle weakness 7
- Severe disturbances of muscle function 7
- Chronic CNS toxicity 7
- Increased excretion of acylcarnitines in urine 4, 5, 6
Treatment and Management
Treatment with L-carnitine may be undertaken, but its effectiveness varies:
- L-carnitine supplementation may prevent the fall in plasma carnitine and result in greater increases in excretion of acylcarnitines 5
- Exercise tolerance in MCAD-deficient patients may be improved by short-term L-carnitine supplementation 5
- However, L-carnitine supplementation may not always prove effective, and avoidance of fasting and prompt institution of glucose supplementation remain the mainstays of therapy for MCAD-deficient patients 4