Neonatal Long-Chain 3-Ketoacyl-CoA Thiolase deficiency: Clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiography.

Autor:	Veenvliet ARJ; Radboudumc Amalia Children's Hospital, Radboud Center for Mitochondrial Medicine, Nijmegen, the Netherlands., Garrelfs MR; Radboudumc Amalia Children's Hospital, Radboud Center for Mitochondrial Medicine, Nijmegen, the Netherlands., Udink Ten Cate FEA; Academic Center for Congenital Heart Disease (ACAHA), Department of Pediatric Cardiology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands., Ferdinandusse S; Laboratory Genetic Metabolic Diseases; Amsterdam Gastroenterology, Endocrinology and Metabolism institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Denis S; Laboratory Genetic Metabolic Diseases; Amsterdam Gastroenterology, Endocrinology and Metabolism institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Fuchs SA; Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.; United for Metabolic Diseases, the Netherlands., Schwantje M; Laboratory Genetic Metabolic Diseases; Amsterdam Gastroenterology, Endocrinology and Metabolism institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands., Geurtzen R; Amalia Childrens Hospital, department of neonatology, Radboud University Medical Center, Nijmegen, the Netherlands., van Wegberg AMJ; Department of Gastroenterology and Hepatology, Dietetics and Intestinal Failure, Radboud University Medical Center, Nijmegen, the Netherlands., Huigen MCDG; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Kluijtmans LAJ; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Wanders RJA; United for Metabolic Diseases, the Netherlands.; Laboratory Genetic Metabolic Diseases; Amsterdam Gastroenterology, Endocrinology and Metabolism institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.; Departments of Pediatrics and Human Genetics, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, the Netherlands., Derks TGJ; United for Metabolic Diseases, the Netherlands., de Boer L; Radboudumc Amalia Children's Hospital, Radboud Center for Mitochondrial Medicine, Nijmegen, the Netherlands.; United for Metabolic Diseases, the Netherlands., Houtkooper RH; United for Metabolic Diseases, the Netherlands.; Laboratory Genetic Metabolic Diseases; Amsterdam Gastroenterology, Endocrinology and Metabolism institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands., de Vries MC; Radboudumc Amalia Children's Hospital, Radboud Center for Mitochondrial Medicine, Nijmegen, the Netherlands.; United for Metabolic Diseases, the Netherlands., van Karnebeek CDM; Radboudumc Amalia Children's Hospital, Radboud Center for Mitochondrial Medicine, Nijmegen, the Netherlands.; United for Metabolic Diseases, the Netherlands.; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.; Departments of Pediatrics and Human Genetics, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Molecular genetics and metabolism reports [Mol Genet Metab Rep] 2022 May 04; Vol. 31, pp. 100873. Date of Electronic Publication: 2022 May 04 (Print Publication: 2022).
DOI:	10.1016/j.ymgmr.2022.100873
Abstrakt:	Isolated long-chain 3-keto-acyl CoA thiolase (LCKAT) deficiency is a rare long-chain fatty acid oxidation disorder caused by mutations in HADHB. LCKAT is part of a multi-enzyme complex called the mitochondrial trifunctional protein (MTP) which catalyzes the last three steps in the long-chain fatty acid oxidation. Until now, only three cases of isolated LCKAT deficiency have been described. All patients developed a severe cardiomyopathy and died before the age of 7 weeks. Here, we describe a newborn with isolated LCKAT deficiency, presenting with neonatal-onset cardiomyopathy, rhabdomyolysis, hypoglycemia and lactic acidosis. Bi-allelic 185G > A (p.Arg62His) and c1292T > C (p.Phe431Ser) mutations were found in HADHB . Enzymatic analysis in both lymphocytes and cultured fibroblasts revealed LCKAT deficiency with a normal long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD, also part of MTP) enzyme activity. Clinically, the patient showed recurrent cardiomyopathy, which was monitored by speckle tracking echocardiography. Subsequent treatment with special low-fat formula, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT) and ketone body therapy in (sodium-D,L-3-hydroxybutyrate) was well tolerated and resulted in improved carnitine profiles and cardiac function. Resveratrol, a natural polyphenol that has been shown to increase fatty acid oxidation, was also considered as a potential treatment option but showed no in vitro benefits in the patient's fibroblasts. Even though our patient deceased at the age of 13 months, early diagnosis and prompt initiation of dietary management with addition of sodium-D,L-3-hydroxybutyrate may have contributed to improved cardiac function and a much longer survival when compared to the previously reported cases of isolated LCKAT-deficiency. Competing Interests: We have no conflicts of interest to report. (© 2022 The Authors.)
Databáze:	MEDLINE
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