Clinical characteristics of primary carnitine deficiency: A structured review using a case‐by‐case approach

Abstract

A broad spectrum of signs and symptoms has been attributed to primary carnitine deficiency (PCD) since its first description in 1973. Advances in diagnostic procedures have improved diagnostic accuracy and the introduction of PCD in newborn screening (NBS) programs has led to the identification of an increasing number of PCD patients, including mothers of screened newborns, who may show a different phenotype compared to clinically diagnosed patients. To elucidate the spectrum of signs and symptoms in PCD patients, we performed a structured literature review. Using a case‐by‐case approach, clinical characteristics, diagnostic data, and mode of patient identification were recorded. Signs and symptoms were categorized by organ involvement. In total, 166 articles were included, reporting data on 757 individual patients. In almost 20% (N = 136) of the cases, the diagnosis was based solely on low carnitine concentration which we considered an uncertain diagnosis of PCD. The remaining 621 cases had a diagnosis based on genetic and/or functional (ie, carnitine transporter activity) test results. In these 621 cases, cardiac symptoms (predominantly cardiomyopathy) were the most prevalent (23.8%). Neurological (7.1%), hepatic (8.4%), and metabolic (9.2%) symptoms occurred mainly in early childhood. Adult onset of symptoms occurred in 16 of 194 adult patients, of whom 6 (3.1%) patients suffered a severe event without any preceding symptom (five cardiac events and one coma). In conclusion, symptoms in PCD predominantly develop in early childhood. Most newborns and mothers of newborns detected through NBS remain asymptomatic. However, though rarely, severe complications do occur in both groups.

Cardiologic evaluation of Turkish mitochondrial fatty acid oxidation disorders

“…In our patient group, dilated and hypertrophic cardiomyopathy were observed with a similar frequency. Although arrhythmias such as long QT syndrome, ventricular fibrillation, ventricular tachycardia, and short-QT were reported, 10,[12][13][14] there was no patient with clinical symptoms of such arrhythmias in our cohort.…”

Newborn Screening of Primary Carnitine Deficiency: An Overview of Worldwide Practices and Pitfalls to Define an Algorithm before Expansion of Newborn Screening in France

“…However, when OCTN2 function is impaired, a major urinary leak of free carnitine leads to a progressively significant decrease in both intracellular and circulating carnitine concentrations, resulting in PCD. Clinical characteristics of PCD encompass a broad clinical spectrum and have been widely assessed in high quality reviews [ 8 , 9 , 10 , 11 ]. In absence of newborn screening (NBS), patients usually present in their infancy: acute metabolic decompensation with hypoketotic hypoglycemia; dilated cardiomyopathy; and hepatic cytolysis.…”

“…Without L-carnitine treatment, death can occur due to heart failure. Fortunately, PCD has an excellent prognosis upon L-carnitine supplementation and almost all patients remain asymptomatic [ 11 ]. Incidence of primary carnitine deficiency was quite variable depending on the studied population, ranging from 1:300 in the Faroe Islands [ 12 ] where there was a founding mutation, to 1:30-142,000 in Japan, Australia, or USA [ 13 , 14 , 15 ].…”

Primary carnitine deficiency is a life‐long disease

“…Defects in OCTN2 lead to significant decreases in intracellular carnitine availability, which may impair mitochondrial fatty acid oxidation 4–6 . The disease can present early in life with acute hypoketotic hypoglycaemia, cardiomyopathy and sudden cardiac death 7 . The condition is treatable with lifelong carnitine supplementation.…”

“… 4 , 5 , 6 The disease can present early in life with acute hypoketotic hypoglycaemia, cardiomyopathy and sudden cardiac death. 7 The condition is treatable with lifelong carnitine supplementation.…”