Title :

Serum succinate/fumarate ratio in paraganglioma/pheochromocytoma patients attending an endocrine oncogenetic unit.

Author(s) :

Bancel, Leo-Paul [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Masso, Vincent [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Dessein, Anne-Frédérique [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Aubert, Sebastien [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Leteurtre, Emmanuelle [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Coppin, Lucie [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Odou, Marie-Francoise [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Do Cao, Christine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Cardot-Bauters, Catherine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Pigny, Pascal [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]

Journal title :

Journal of Clinical Endocrinology and Metabolism

Publisher :

Endocrine Society

Publication date :

2023-03-01

ISSN :

0021-972X

English keyword(s) :

paraganglioma
pheochromocytoma
SDH
succinate
fumarate
enzyme deficiency

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

ContextPheochromocytomas and paragangliomas (PPGLs) with SDHx pathogenic variants (PVs) are characterized by a higher intratissular succinate/fumarate ratio (RS/F) than non-SDHx–mutated ones. Also, an increase in serum ...
Show more >ContextPheochromocytomas and paragangliomas (PPGLs) with SDHx pathogenic variants (PVs) are characterized by a higher intratissular succinate/fumarate ratio (RS/F) than non-SDHx–mutated ones. Also, an increase in serum succinate levels has been reported in patients with germline SDHB or SDHD PV.ObjectiveTo assess whether measurement of serum succinate, fumarate levels, and RS/F might aid identification of an SDHx germline PV/likely pathogenic variant (LPV) in patients with PPGL or in asymptomatic relatives; and to guide identification of a PV/LPV among the variants of unknown significance (VUS) identified in SDHx by next-generation sequencing.MethodsThis prospective monocentric study included 93 patients attending an endocrine oncogenetic unit for genetic testing. Succinate and fumarate were measured in serum by gas chromatography coupled to mass spectrometry. The RS/F was calculated to assess SDH enzymatic function. Diagnostic performance was assessed by receiver operating characteristic analysis.ResultsRS/F had a higher discriminant power than succinate alone to identify an SDHx PV/LPV in patients with PPGL. However, SDHD PVs/LPVs are frequently missed. Only RS/F differed between asymptomatic SDHB/SDHD PV/LPV carriers and SDHB/SDHD-linked patients with PPGL. Finally RS/F could be helpful to easily evaluate the functional impact of VUS in SDHx.ConclusionMeasurement of serum RS/F in patients with PPGL and in asymptomatic relatives is a valuable initial workup tool to detect those carrying a germline PV/LPV in SDHx. Its discriminative power is equal or superior to those of succinate measured alone. SDHD PVs/LPVs are less frequently identified by these biochemical tools. Use of RS/F for SDHx VUS reclassification needs to be evaluated further.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Collections :

• Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (MSAP) - USR 3290

Source :

Harvested from HAL