Long-term liver disease in methylmalonic and propionic acidemias.

Détails

ID Serval
serval:BIB_811CC7F41074
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Long-term liver disease in methylmalonic and propionic acidemias.
Périodique
Molecular genetics and metabolism
Auteur(s)
Imbard A., Garcia Segarra N., Tardieu M., Broué P., Bouchereau J., Pichard S., de Baulny H.O., Slama A., Mussini C., Touati G., Danjoux M., Gaignard P., Vogel H., Labarthe F., Schiff M., Benoist J.F.
ISSN
1096-7206 (Electronic)
ISSN-L
1096-7192
Statut éditorial
Publié
Date de publication
04/2018
Peer-reviewed
Oui
Volume
123
Numéro
4
Pages
433-440
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Patients affected with methylmalonic acidemia (MMA) and propionic acidemia (PA) exhibit diverse long-term complications and poor outcome. Liver disease is not a reported complication. The aim of this study was to characterize and extensively evaluate long-term liver involvement in MMA and PA patients.
We first describe four patients who had severe liver involvement during the course of their disease. Histology showed fibrosis and/or cirrhosis in 3 patients. Such liver involvement led us to retrospectively collect liver (clinical, laboratory and ultrasound) data of MMA (N = 12) or PA patients (N = 16) from 2003 to 2016.
Alpha-fetoprotein (αFP) levels were increased in 8/16 and 3/12 PA and MMA patients, respectively, and tended to increase with age. Moderate and recurrent increase of GGT was observed in 4/16 PA patients and 4/12 MMA patients. Abnormal liver ultrasound with either hepatomegaly and/or hyperechoic liver was observed in 7/9 PA patients and 3/9 MMA patients.
These data demonstrate that approximately half of the patients affected by MMA or PA had signs of liver abnormalities. The increase of αFP with age suggests progressive toxicity, which might be due to the metabolites accumulated in PA and MMA. These metabolites (e.g., methylmalonic acid and propionic acid derivatives) have previously been reported to have mitochondrial toxicity; this toxicity is confirmed by the results of histological and biochemical mitochondrial analyses of the liver in two of our MMA patients. In contrast to the moderate clinical, laboratory or ultrasound expression, severe pathological expression was found for three of the 4 patients who underwent liver biopsy, ranging from fibrosis to cirrhosis. These results emphasize the need for detailed liver function evaluation in organic aciduria patients, including liver biopsy when liver disease is suspected.
MMA and PA patients exhibit long-term liver abnormalities.
Mots-clé
Alpha-fetoprotein, Hepatomegaly, Liver disease, Liver fibrosis, MMA, OXPHOS deficiency, Organic acidemias, PA
Pubmed
Web of science
Création de la notice
15/02/2018 20:59
Dernière modification de la notice
23/05/2018 6:15
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