Primary carnitine deficiency, a form of long chain fatty acid oxidation disorder, paralyzes the ability of carnitine to be transported across plasma membranes into cells. The resulting picture is the pathological decrease of intracellular carnitine concentrations, impairing mitochondrial fatty acid oxidation. 

In recent decades, our understanding of primary carnitine deficiency has improved by leaps and bounds. Initially, the main diagnostic criteria for this condition was low carnitine concentration in the muscle or the blood. However, scientists subsequently discovered the transporter responsible for carnitine transport. They also discovered that variants in the encoding gene (SLC22A5) impair carnitine transportation across plasma membranes. 

“Subsequently, it has become common practice to diagnose [primary carnitine deficiency] patients based on biallelic pathogenic variants in SLC22A5, and/or reduced carnitine transporter activity measured in fibroblasts,” Crefcoeur and colleagues wrote in the Journal of Inherited Metabolic Disease. 

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Primary carnitine deficiency can often result in multisystemic damage. For example, cardiomyopathy is present in an estimated 1 out of every 5 of patients with this condition. Neurological conditions, such as encephalopathy, occur in around 6% of patients. Hepatomegaly and hepatic steatosis have been reported in approximately 7% of patients with primary carnitine deficiency. Around 7% of patients experience muscle weakness. 

Read more about long chain fatty acid oxidation disorder etiology 

It may come as a surprise that low carnitine levels can be responsible for pathology on so many fronts. This has prompted physicians to call for newborn screening programs for this condition to be expanded. Studies show that primary carnitine deficiency detected via newborn screening results in better outcomes; this is likely because early detection usually translates to early treatment. 

“The disease can present early in life with acute hypoketotic hypoglycemia, cardiomyopathy, and sudden cardiac death,” Crefcoeur et al wrote in JMID Reports. “The condition is treatable with lifelong carnitine supplementation.” 

Case Study: Long-Term Follow Up in Patient With Primary Carnitine Deficiency 

Crefcoeur et al presented the case of an 18-month-old male who presented with lower respiratory tract infection and congestive heart failure. He was admitted for close observation. A cardiac ultrasound revealed that the child had a dilated left ventricle with poor contractility. 

Laboratory investigations revealed extremely low serum free carnitine levels (1.4 μmol/L), while urinary carnitine concentration was increased. This combination of signs was indicative of primary carnitine deficiency. This diagnosis was later confirmed genetically and functionally. 

His physicians started him on L-carnitine (3TD 500 mg daily), diuretics, and antibiotics. Within 3 months, the patient’s cardiac function normalized; after that, only carnitine supplementation was continued. In subsequent follow ups, physicians detected no change in his left ventricular ejection fraction. 

However, at the age of 13, the patient stopped taking his medication, despite advice from his parents and caretaker not to do so. Nevertheless, he participated in the Muslim fast of Ramadan (abstaining from food and drink from dawn to sunset) every year.

At 27 years of age, the patient decided to withdraw from medical follow-up completely. His last left ventricular ejection fraction on record was 50%, and serum-free carnitine levels remained low at 4.0 μmol/L. 

At 29 years of age, the patient presented again with heart failure and atrial fibrillation, which his physicians attributed to a bout of viral respiratory tract infection. Ultrasound revealed a dilated heart with severe mitral valve insufficiency and a marked decrease in cardiac function. His physicians prescribed him diuretics, inotropes, and L-carnitine. Two weeks later, his left ventricular ejection fraction improved to 30%, and he was enrolled in a cardiac rehabilitation program. He continued to attend cardiology follow-up; 5 years later, his left ventricular ejection fraction improved to 57%, and he only had moderate mitral valve insufficiency. 

At 38 years of age, the patient was approached to participate in a study on primary carnitine deficiency. Scientists once again measured his carnitine levels, which were low (14 μmol/L), despite being on carnitine supplementation of 4TD 3g. Cardiac evaluations revealed a slightly dilated left ventricle and no arrhythmias. His physicians deemed him unfit for work. 

The Importance of Treatment Compliance

This case study indicates that the cumulative effect of discontinuing carnitine supplementation against medical advice can result in severe complications years later. 

The authors of this study pointed out that some young people have a superficial understanding of what it means to be “well”; oftentimes, “health” is seen as a subjective feeling instead of an objective fact. This is worrying, because refusing medical advice on these faulty grounds can result in long-term consequences. 

“It is likely that, with continued treatment and follow-up, the second cardiac decompensation could have been prevented,” the authors of the study wrote. 

Read more about long chain fatty acid oxidation disorder treatment 

There is no escaping the reality that primary carnitine deficiency is a lifelong illness that requires close monitoring and follow-up. Should patients forego the medications prescribed, other healthcare providers should step in to once again urge compliance. One of the best ways to do this is to ensure that a patient’s medical records are up-to-date so that other practitioners can gauge whether the patient has been compliant to the medications prescribed. 

“In conclusion, patients with [primary carnitine deficiency] that feel “healthy” following successful treatment during childhood years, may be prone to disregard their disease and important medication to maintain their health,” Crefcoeur et al wrote. “Treatment cessation in primary carnitine deficiency can lead to severe heart failure, even decades later.” 


Crefcoeur LL, Melles MC, Bruning TA, et al. Primary carnitine deficiency is a life-long diseaseJIMD Rep. Published online July 27, 2022. doi:10.1002/jmd2.12319

Crefcoeur LL, Visser G, Ferdinandusse S, et al. Clinical characteristics of primary carnitine deficiency: a structured review using a case-by-case approachJ Inherit Metab Dis. Published online January 8, 2022. doi:10.1002/jimd.12475