Does a low carnitine level in a dry blood test indicate a systemic carnitine deficiency?

From the Guidelines

A low carnitine level in a dry blood test does not necessarily indicate systemic carnitine deficiency, and a definitive diagnosis requires additional testing, including plasma carnitine measurements and genetic testing for mutations in the SLC22A5 gene. While dry blood spot testing can detect low carnitine levels, carnitine levels can be temporarily low due to factors like dietary restrictions, certain medications, or sample handling issues 1. If low carnitine is detected on a dry blood test, follow-up testing should include comprehensive plasma carnitine profile (measuring both free and total carnitine), urinary carnitine excretion, and possibly genetic testing.

Key Considerations

• Systemic carnitine deficiency is a rare metabolic disorder affecting carnitine transport, which is essential for fatty acid metabolism.
• Treatment typically involves L-carnitine supplementation at doses of 2-5 mg/kg/day, as suggested by the ESPEN micronutrient guideline, until carnitine and acyl-to-free ratio revert to normal values 1.
• Patients with confirmed deficiency require lifelong supplementation and should avoid fasting and high-fat diets to prevent metabolic decompensation.
• The administration of carnitine supplementation should be considered in patients on prolonged PN and prolonged continuous renal replacement therapy, with a systematic supplementation of 0.5-1 g/day 1.

Important Factors to Consider

• The use of L-carnitine in patients with low serum free L-carnitine concentrations, such as those undergoing dialysis, may be beneficial in improving nutritional status and reducing symptoms like anemia, cardiomyopathy, and muscle weakness 1.
• However, the evidence for the routine use of L-carnitine in these patients is insufficient, and its use should be considered on a case-by-case basis, taking into account the individual patient's symptoms and response to standard therapies 1.

From the FDA Drug Label

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.

A low carnitine level in a dry blood test may indicate a systemic carnitine deficiency, as carnitine deficiency is defined by abnormally low plasma concentrations of free carnitine. However, the diagnosis of systemic carnitine deficiency should be based on plasma concentrations of free carnitine, and the dry blood test result should be interpreted in the context of other clinical and laboratory findings 2.

• Key points:
  • Low plasma concentrations of free carnitine (< 20 μmol/L) may indicate carnitine deficiency
  • Systemic carnitine deficiency may be associated with low tissue and/or urine concentrations
  • Diagnosis should be based on plasma concentrations of free carnitine and other clinical and laboratory findings

From the Research

Low Carnitine Levels in Dry Blood Test

• A low carnitine level in a dry blood test may indicate a systemic carnitine deficiency, as seen in primary systemic carnitine deficiency (SCD) 3, 4.
• Systemic primary carnitine deficiency is a rare autosomal recessive disorder caused by a defect in plasma membrane uptake of carnitine due to SLC22A5 gene mutations 4, 5.
• The clinical manifestations of SCD can vary widely, but are typically characterized by episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal myopathy, elevated creatine kinase (CK), and cardiomyopathy in childhood; or cardiomyopathy, arrhythmias, or fatigability in adulthood 4.

Diagnosis and Treatment

• The diagnosis of SCD can be suspected on newborn screening, but is established by demonstration of low plasma free carnitine concentration, reduced fibroblast carnitine transport, and molecular testing of the SLC22A5 gene 4.
• Treatment involves supplementation of oral levocarnitine (L-carnitine) at a dose of 50-400 mg/kg/day divided into three doses, which can improve clinical outcome and normalize liver size and enzymes 4, 5.
• Regular monitoring, including annual echocardiogram and electrocardiogram, frequent plasma carnitine levels, and CK and liver transaminases measurement, is recommended to manage the condition effectively 4.

Case Studies

• Several case studies have reported the effectiveness of L-carnitine supplementation in improving clinical outcomes in patients with SCD, including a 6-year-old girl with primary systemic carnitine deficiency who showed improved health with resolving cardiomyopathy after L-carnitine therapy 3.
• A 9-month-old boy with hypertrophic cardiomyopathy and massive hepatomegaly due to SCD showed improved clinical outcome with ejection fraction to 75% and normalization of liver size and enzymes after 3 months of oral carnitine supplementation 5.
• A Korean patient with SCD confirmed by biochemical and molecular investigation showed normalized plasma free carnitine level and remained asymptomatic after L-carnitine supplement 6.