From the Guidelines
To diagnose carnitine deficiency, blood tests measuring free and total carnitine levels, as well as the acyl-to-free carnitine ratio, are essential, with a ratio greater than 0.4 confirming the diagnosis, as recommended by the most recent guideline 1. The diagnosis of carnitine deficiency requires laboratory tests to confirm low levels of carnitine in the body. The following tests are necessary:
- Free and total carnitine levels in blood
- Acyl-to-free carnitine ratio, which should be calculated from the free and total carnitine levels, with a ratio greater than 0.4 indicating carnitine deficiency, as stated in the guideline 1
- Additional tests, such as liver function tests, glucose, lactate, ammonium, and urine ketones, may be necessary to investigate suspected deficiency, as mentioned in the guideline 1 These tests should be performed in a specialist laboratory facility, as they require specific equipment and expertise, such as tandem mass spectrometry (MS/MS) stable isotope dilution analysis, as described in the guideline 1. It is crucial to diagnose carnitine deficiency before symptoms become severe, as carnitine plays a vital role in fatty acid transport into mitochondria for energy production, and deficiency can lead to energy deficits, particularly in high-energy tissues like the heart and skeletal muscle, resulting in symptoms like muscle weakness, cardiomyopathy, and hypoglycemia. The most recent guideline recommends measuring the simultaneous concentrations of total carnitine, free carnitine, carnitine esters, and the carnitine precursors to enable the calculation of the acyl-to-free carnitine ratio, which should only be used to confirm a clinical diagnosis and should not delay commencing supplements, as stated in the guideline 1.
From the FDA Drug Label
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 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.
The laboratory tests needed to diagnose carnitine (L-carnitine) deficiency include:
- Serum carnitine levels
- Red cell carnitine levels
- Tissue carnitine levels
- Urine carnitine concentrations
- Plasma concentration ratio of acylcarnitine/levocarnitine 2 2
From the Research
Laboratory Tests for Carnitine Deficiency
To diagnose carnitine (L-carnitine) deficiency, several laboratory tests are necessary. These tests help establish the diagnosis and differentiate primary carnitine deficiency from secondary causes.
- Newborn Screening: The diagnosis can be suspected on newborn screening 3.
- Plasma Free Carnitine Concentration: Demonstration of low plasma free carnitine concentration (<5 μM, normal 25-50 μM) is essential for diagnosis 3.
- Fibroblast Carnitine Transport: Reduced fibroblast carnitine transport (<10% of controls) is a key diagnostic criterion 3.
- Molecular Testing of the SLC22A5 Gene: Molecular testing of the SLC22A5 gene is necessary to confirm the diagnosis and identify causative variants 3, 4.
- Echocardiogram and Electrocardiogram: An echocardiogram and electrocardiogram should be performed for baseline assessment once the diagnosis is established 3.
- CK Concentration and Liver Transaminases Measurement: CK concentration and liver transaminases measurement should be performed for baseline assessment 3.
- Pre-prandial Blood Sugar Levels: Pre-prandial blood sugar levels should be measured for baseline assessment 3.
Additional Tests
Additional tests may be necessary to monitor the patient's condition and response to treatment. These include:
- Annual Echocardiogram and Electrocardiogram: Annual echocardiogram and electrocardiogram are recommended for surveillance 3.
- Frequent Plasma Carnitine Levels: Frequent plasma carnitine levels should be measured to monitor the patient's response to treatment 3.
- CK and Liver Transaminases Measurement: CK and liver transaminases measurement can be considered during acute illness 3.