What are the differences between primary myopathic carnitine deficiency and systemic carnitine deficiency?

From the Guidelines

Primary myopathic carnitine deficiency and systemic carnitine deficiency are two distinct disorders with different clinical presentations, genetic basis, and treatment approaches. The main difference between primary myopathic carnitine deficiency and systemic carnitine deficiency lies in the extent of carnitine deficiency and the tissues affected. Primary myopathic carnitine deficiency is characterized by decreased carnitine levels specifically in muscle tissue, while maintaining normal blood carnitine levels, and typically presents with isolated muscle weakness, exercise intolerance, and myalgia, primarily affecting skeletal muscles 1. In contrast, systemic carnitine deficiency involves defective carnitine transport across all tissues, resulting in low carnitine levels throughout the body, including blood, muscle, and other tissues, and presents with more severe and widespread manifestations, including cardiomyopathy, hypoglycemia, hepatomegaly, and encephalopathy, in addition to muscle weakness 1.

Key differences between primary myopathic and systemic carnitine deficiency

• Clinical presentation: Primary myopathic carnitine deficiency presents with isolated muscle weakness, exercise intolerance, and myalgia, while systemic carnitine deficiency presents with more severe and widespread manifestations, including cardiomyopathy, hypoglycemia, hepatomegaly, and encephalopathy.
• Genetic basis: Systemic carnitine deficiency is an autosomal recessive disorder with identifiable mutations in the SLC22A5 gene, while myopathic deficiency may have various genetic or acquired causes.
• Treatment approaches: Myopathic deficiency may respond to moderate carnitine supplementation (1-2 g/day), while systemic deficiency requires higher doses (100-400 mg/kg/day) of oral L-carnitine supplementation for life.
• Tissue involvement: Primary myopathic carnitine deficiency affects muscle tissue specifically, while systemic carnitine deficiency affects all tissues, including blood, muscle, and other tissues.

According to the most recent and highest quality study, the diagnosis of carnitine deficiency is confirmed by measurements of plasma free and total carnitine with an acyl:free carnitine ratio greater than 0.4 or a total serum carnitine value less than 40 μmol/L 1. Additionally, carnitine deficiency can result in the development of anemia, cardiomyopathy, and muscle weakness, all symptoms that may be present in the dialysis population 1.

From the FDA Drug Label

Primary systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues A diagnosis of primary carnitine deficiency requires that serum, red cell and/or tissue carnitine levels be low and that the patient does not have a primary defect in fatty acid or organic acid oxidation

The main difference between primary myopathic carnitine deficiency and systemic carnitine deficiency is not explicitly stated in the provided drug labels.

• Systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues.
• The term primary myopathic carnitine deficiency is not mentioned in the provided drug labels, therefore, no conclusion can be drawn about its differences with systemic carnitine deficiency 2 2.

From the Research

Differences between Primary Myopathic Carnitine Deficiency and Systemic Carnitine Deficiency

• Primary myopathic carnitine deficiency is characterized by low carnitine concentrations usually restricted to muscle 3
• Systemic carnitine deficiency shows decreased concentrations in other organs and plasma as well 3
• Systemic carnitine deficiency features recurrent metabolic crises similar to those seen in Reye's syndrome and nonketotic hypoglycemia 3
• Primary myopathic carnitine deficiency is a predominantly myopathic form, with normal serum and low muscle carnitine levels 4
• Systemic form of carnitine deficiency has encephalopathy, hepatic dysfunction, muscle weakness and low muscle, liver and serum carnitine levels 4

Clinical Manifestations

• Systemic primary carnitine deficiency (CDSP) can vary widely with respect to age of onset, organ involvement, and severity of symptoms 5
• CDSP is typically characterized by episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants 5
• Skeletal myopathy, elevated creatine kinase (CK), and cardiomyopathy in childhood 5
• Cardiomyopathy, arrhythmias, or fatigability in adulthood 5
• Primary myopathic carnitine deficiency may present with myalgia and muscular fatigability during prolonged physical exercise 6

Diagnosis and Treatment

• Diagnosis of CDSP is established by demonstration of low plasma free carnitine concentration, reduced fibroblast carnitine transport, and molecular testing of the SLC22A5 gene 5
• Primary treatment involves supplementation of oral levocarnitine (L-carnitine) at a dose of 50-400 mg/kg/day divided into three doses 5
• Therapeutic measures used in primary myopathic carnitine deficiency have included prednisone, carnitine replacement and a low-fat with medium chain tryglycerides and high-carbohydrate diet 4
• Oral therapy with L-carnitine (3 g per day) resolved the clinical symptoms completely in adult patients with primary myopathic carnitine deficiency 6