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Rev Endocr Metab Disord. 2018 Mar;19(1):93-106. doi: 10.1007/s11154-018-9448-1.

Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle.

Author information

1
Dutch Fatty Acid Oxidation Expertise Center, Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584, EA, Utrecht, The Netherlands.
2
Dutch Fatty Acid Oxidation Expertise Center, Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
3
Dutch Fatty Acid Oxidation Expertise Center, Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584, EA, Utrecht, The Netherlands. gvisser4@umcutrecht.nl.
4
Dutch Fatty Acid Oxidation Expertise Center, Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands. gvisser4@umcutrecht.nl.
5
Dutch Fatty Acid Oxidation Expertise Center, Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands. r.h.houtkooper@amc.nl.

Abstract

Mitochondrial fatty acid oxidation is an essential pathway for energy production, especially during prolonged fasting and sub-maximal exercise. Long-chain fatty acids are the most abundant fatty acids in the human diet and in body stores, and more than 15 enzymes are involved in long-chain fatty acid oxidation. Pathogenic mutations in genes encoding these enzymes result in a long-chain fatty acid oxidation disorder in which the energy homeostasis is compromised and long-chain acylcarnitines accumulate. Symptoms arise or exacerbate during catabolic situations, such as fasting, illness and (endurance) exercise. The clinical spectrum is very heterogeneous, ranging from hypoketotic hypoglycemia, liver dysfunction, rhabdomyolysis, cardiomyopathy and early demise. With the introduction of several of the long-chain fatty acid oxidation disorders (lcFAOD) in newborn screening panels, also asymptomatic individuals with a lcFAOD are identified. However, despite early diagnosis and dietary therapy, a significant number of patients still develop symptoms emphasizing the need for individualized treatment strategies. This review aims to function as a comprehensive reference for clinical and laboratory findings for clinicians who are confronted with pediatric and adult patients with a possible diagnosis of a lcFAOD.

KEYWORDS:

Carnitine transport; Inborn errors of metabolism; Mitochondrial long-chain fatty acid oxidation; ß-oxidation

PMID:
29926323
PMCID:
PMC6208583
DOI:
10.1007/s11154-018-9448-1
[Indexed for MEDLINE]
Free PMC Article

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