Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options.

Détails

ID Serval
serval:BIB_8D13263282C7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options.
Périodique
Journal of Inherited Metabolic Disease
Auteur(s)
Staufner C., Lindner M., Dionisi-Vici C., Freisinger P., Dobbelaere D., Douillard C., Makhseed N., Straub B.K., Kahrizi K., Ballhausen D., la Marca G., Kölker S., Haas D., Hoffmann G.F., Grünert S.C., Blom H.J.
ISSN
1573-2665 (Electronic)
ISSN-L
0141-8955
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
39
Numéro
2
Pages
273-283
Langue
anglais
Résumé
BACKGROUND: Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.
METHODS: Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.
RESULTS: The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.
CONCLUSION: Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.
Pubmed
Web of science
Création de la notice
11/03/2016 10:45
Dernière modification de la notice
03/03/2018 19:15
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