Hereditary carnitine deficiency myopathy

Hereditary Carnitine Deficiency Myopathy

Hereditary Carnitine Deficiency Myopathy is a rare genetic disorder characterized by a deficiency in carnitine, a substance essential for the transport of fatty acids into the mitochondria for energy production. This condition primarily affects skeletal muscle, leading to muscle weakness and other systemic symptoms.

Pathophysiology

Carnitine is a quaternary ammonium compound that plays a critical role in the transport of long-chain fatty acids across the inner mitochondrial membrane. In individuals with hereditary carnitine deficiency myopathy, mutations in genes responsible for carnitine transport or metabolism lead to insufficient levels of carnitine in muscle tissues. This results in impaired fatty acid oxidation and energy production, particularly during periods of fasting or increased energy demand.

Genetics

Hereditary Carnitine Deficiency Myopathy is often inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. The most commonly implicated gene is the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2), a protein crucial for carnitine uptake in cells.

Clinical Presentation

Patients with hereditary carnitine deficiency myopathy typically present with:

• Progressive muscle weakness, particularly in the proximal muscles
• Exercise intolerance
• Hypotonia (reduced muscle tone)
• Cardiomyopathy in severe cases
• Hypoglycemia, especially during fasting

Diagnosis

Diagnosis of hereditary carnitine deficiency myopathy involves a combination of clinical evaluation, biochemical tests, and genetic testing. Key diagnostic steps include:

• Measurement of plasma carnitine levels, which are typically low
• Muscle biopsy showing lipid accumulation
• Genetic testing to identify mutations in the SLC22A5 gene or other related genes

Management

Management of hereditary carnitine deficiency myopathy focuses on dietary supplementation and lifestyle modifications:

• Oral carnitine supplementation to restore normal carnitine levels
• High-carbohydrate, low-fat diet to reduce reliance on fatty acid oxidation
• Avoidance of fasting and prolonged exercise

Prognosis

With early diagnosis and appropriate management, individuals with hereditary carnitine deficiency myopathy can lead relatively normal lives. However, untreated cases may result in severe muscle weakness and cardiac complications.

Also see

• Carnitine palmitoyltransferase II deficiency
• Fatty acid oxidation disorders
• Mitochondrial myopathy
• Metabolic myopathy