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Review
. 2022 May;45(3):386-405.
doi: 10.1002/jimd.12475. Epub 2022 Feb 3.

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

Loek L Crefcoeur  1   2 , Gepke Visser  1   2 , Sacha Ferdinandusse  2 , Frits A Wijburg  3 , Mirjam Langeveld  4 , Barbara Sjouke  4
Affiliations
Review

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

Loek L Crefcoeur et al. J Inherit Metab Dis. 2022 May.

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.

Keywords: carnitine; clinical characteristics; organic cation transporter novel 2; phenotyping; primary carnitine deficiency; screening.

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Conflict of interest statement

Mirjam Langeveld is involved in premarketing studies with Sanofi‐Genzyme, Protalix BioTherapeutics, and Idorsia. Financial arrangements are made through AMC Research BV. No fees, travel support, or grants were obtained from pharmaceutical industry. Loek L. Crefcoeur, Gepke Visser, Sacha Ferdinandusse, Frits A. Wijburg, and Barbara Sjouke declare that they have no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Timeline of key moments that impacted the (differential) diagnosis of primary carnitine deficiency
FIGURE 2
FIGURE 2
PRISMA flow diagram of literature selection and inclusion
See this image and copyright information in PMC

References

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