A novel HADHA variant associated with an ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
A novel HADHA variant associated with an atypical moderate and late-onset LCHAD deficiency
Auteur(s) :
Dessein, Anne-Frédérique [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Hebbar, Eleonore [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Vamecq, Joseph [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Lebredonchel, Elodie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Devos, Aurore [Auteur]
UF Génopathies, Pharmaco-génétique, Glycobiologie et Dépistage Périnatal [UF Génopathies]
Ghoumid, Jamal [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Mention, Karine [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Hôpital Jeanne de Flandre [Lille]
Dobbelaere, D. [Auteur]
Joncquel, Marie [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Fontaine, Monique [Auteur]
Defoort, Sabine [Auteur]
Service d’Exploration de la Vision et Neuro-ophtalmologie [CHU Lille]
Smirnov, Vassily [Auteur]
Douillard, Claire [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Dhaenens, Claire-Marie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Hebbar, Eleonore [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Vamecq, Joseph [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Lebredonchel, Elodie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Devos, Aurore [Auteur]
UF Génopathies, Pharmaco-génétique, Glycobiologie et Dépistage Périnatal [UF Génopathies]
Ghoumid, Jamal [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Mention, Karine [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Hôpital Jeanne de Flandre [Lille]
Dobbelaere, D. [Auteur]
Joncquel, Marie [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Fontaine, Monique [Auteur]
Defoort, Sabine [Auteur]
Service d’Exploration de la Vision et Neuro-ophtalmologie [CHU Lille]
Smirnov, Vassily [Auteur]
Douillard, Claire [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Dhaenens, Claire-Marie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Titre de la revue :
Molecular Genetics and Metabolism Reports
Nom court de la revue :
Molec. Genet. Metab. Rep.
Numéro :
31
Pagination :
-
Date de publication :
2022-05-17
ISSN :
2214-4269
Mot(s)-clé(s) en anglais :
Mitochondrial trifunctional protein MTP
HADHA
Cardiomyopathy
Atypical maculopathy
Late-onset
LCHAD
HADHA
Cardiomyopathy
Atypical maculopathy
Late-onset
LCHAD
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
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 ...
Lire la suite >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).Lire moins >
Lire la suite >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).Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
- Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
- Lille Neurosciences & Cognition (LilNCog) - U 1172
- Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
- Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Date de dépôt :
2023-06-05T06:59:01Z
2024-04-18T08:50:41Z
2024-04-18T08:50:41Z
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