title: Thymidine phosphorylase gene mutations in patients with mitochondrial neurogastrointestinal encephalomyopathy syndrome.
abstract: The mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is characterized by the association of gastrointestinal and neurological symptoms. It is a rare autosomal recessive mitochondrial disorder with multiple mitochondrial DNA deletions and/or depletion. It is caused by thymidine phosphorylase (TP) gene mutations resulting in a complete abolition of TP activity. We tested 31 unrelated patients presenting either with a complete MNGIE syndrome (8 patients), a severe intestinal pseudo-obstruction (10 patients), and multiple deletions and/or depletion of mitochondrial DNA (13 patients). All the tested patients presenting with a complete MNGIE had increased thymidine levels in plasma and urine, and no TP activity. The group with pseudo-obstruction syndrome had normal or partial reduction of TP activity. We found pathogenic mutations on TP gene only in the MNGIE syndrome group: all the MNGIE patients were compound heterozygous or homozygous for mutations in the TP gene. Eight of these mutations are yet unreported, confirming the lack of genotype/phenotype correlation in this syndrome. Enzymatic activity and thymidine level are thus rapid diagnosis tests to detect MNGIE affected patients prior to genetic testing for patients with gastrointestinal symptoms.
authors.affiliation: Laboratoire de Biochimie 1, AP-HP Hôpital Bicêtre, France. abdel.slama@bct.ap-hop-paris.fr
authors.forename: A
authors.initials: A
authors.lastname: Slama
authors.forename: C
authors.initials: C
authors.lastname: Lacroix
authors.forename: V
authors.initials: V
authors.lastname: Plante-Bordeneuve
authors.forename: A
authors.initials: A
authors.lastname: Lombès
authors.forename: M
authors.initials: M
authors.lastname: Conti
authors.forename: J M
authors.initials: JM
authors.lastname: Reimund
authors.forename: E
authors.initials: E
authors.lastname: Auxenfants
authors.forename: P
authors.initials: P
authors.lastname: Crenn
authors.forename: P
authors.initials: P
authors.lastname: Laforêt
authors.forename: A
authors.initials: A
authors.lastname: Joannard
authors.forename: D
authors.initials: D
authors.lastname: Seguy
authors.forename: H
authors.initials: H
authors.lastname: Pillant
authors.forename: P
authors.initials: P
authors.lastname: Joly
authors.forename: S
authors.initials: S
authors.lastname: Haut
authors.forename: B
authors.initials: B
authors.lastname: Messing
authors.forename: G
authors.initials: G
authors.lastname: Said
authors.forename: A
authors.initials: A
authors.lastname: Legrand
authors.forename: A
authors.initials: A
authors.lastname: Guiochon-Mantel
mesh_terms: D000328:Adult; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D009154:Mutation; D017384:Sequence Deletion; D013577:Syndrome; D013936:Thymidine / Q000097:blood / Q000652:urine; D013939:Thymidine Phosphorylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D013939:Thymidine Phosphorylase; D013936:Thymidine