A novel HADHA variant associated with an atypical moderate and late-onset LCHAD deficiency.

Autor:	Dessein AF; Univ. Lille, CHU Lille, Centre de Biologie Pathologie Génétique, UF Métabolisme Général et Maladies Rares, F-59000 Lille, France., Hebbar E; CHU Lille, Cardiology Department, F-59000 Lille, France., Vamecq J; Inserm, Biochemistry and Molecular Biology Laboratory, HMNO, CBP, CHRU Lille & EA 7364 - RADEME, North France University Lille, F-59000 Lille, France., Lebredonchel E; Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.; Univ. Lille, CHU Lille, Pôle Biologie Pathologie Génétique, Institut de biochimie et de biologie moléculaire, UAM de Glycopathologies, F-59000 Lille, France., Devos A; CHU Lille, Centre de Biologie Pathologie Génétique, UF Génopathies, F-59000 Lille, France., Ghoumid J; CHU Lille, Clinical Genetics Department, Reference Center for Developmental Anomalies, F-59000 Lille, France., Mention K; Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre University Hospital and RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364 CHU Lille, F-59037 Lille, France., Dobbelaere D; Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre University Hospital and RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364 CHU Lille, F-59037 Lille, France., Chevalier-Curt MJ; Univ. Lille, CHU Lille, Centre de Biologie Pathologie Génétique, UF Métabolisme Général et Maladies Rares, F-59000 Lille, France., Fontaine M; Univ. Lille, CHU Lille, Centre de Biologie Pathologie Génétique, UF Métabolisme Général et Maladies Rares, F-59000 Lille, France., Defoort S; CHU Lille, Exploration of Vision and Neuro-ophthalmology department, Lille University Hospital, F-59000 Lille, France., Smirnov V; CHU Lille, Exploration of Vision and Neuro-ophthalmology department, Lille University Hospital, F-59000 Lille, France., Douillard C; Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre University Hospital and RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364 CHU Lille, F-59037 Lille, France.; CHU Lille, Department of Endocrinology and Metabolism, F-59000 Lille, France., Dhaenens CM; Univ. Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, F-59000 Lille, France.
Jazyk:	angličtina
Zdroj:	Molecular genetics and metabolism reports [Mol Genet Metab Rep] 2022 Mar 15; Vol. 31, pp. 100860. Date of Electronic Publication: 2022 Mar 15 (Print Publication: 2022).
DOI:	10.1016/j.ymgmr.2022.100860
Abstrakt:	Background: Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare inherited disease caused by pathogenic variants of HADHA gene. Along with signs common to fatty acid oxidation defects (FAOD), specific retina and heart alterations are observed. Because long-chain fatty acid oxidation is selectively affected, supplementations with short/medium-chain fats represent energetic sources bypassing the enzymatic blockade. Here, we report on an atypical presentation of the disease. Methods: Clinical features were described with medical explorations including ophthalmic and cardiac examination. Biological underlying defects were investigated by measurements of biochemical metabolites and by fluxomic studies of mitochondrial β-oxidation. Whole exome sequencing and molecular validation of variants confirmed the diagnosis. Results: The patient has developed at nine years an unlabeled maculopathy, and at 28 years, an acute cardiac decompensation without any premise. Blood individual acylcarnitine analysis showed a rise in hydroxylated long-chain fatty acids and fluxomic studies validated enzyme blockade consistent with LCHADD. Genetic analysis revealed the common p.(Glu510Gln) variant in HADHA , in trans with a novel variant c.1108G > A, p.(Gly370Arg) located in the NAD binding domain. Patient pathology was responsive to triheptanoin supplementation. Conclusion: This atypical LCHADD form report should encourage the early assessment of biochemical and genetic testing as a specific management is recommended (combination with fast avoidance, low fat-high carbohydrate diet, medium-even-chain triglycerides or triheptanoin supplementation). Competing Interests: No conflicting relationship exists for any author. (© 2022 The Authors.)
Databáze:	MEDLINE
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