Mitochondrial neurogastrointestinal encephalomyo pathy (MNGIE) in a Malaysian patient with a novel mutation in thymidine phosphorylase gene: A case report
- Author:
Kay Sin Tan
;
Heng Gee Lee
;
Lay Hoong Lian
;
Ying Shean Lu
;
Bee Chin Chen
;
Chee Woon Wang
;
Jayaram Menon
- Publication Type:Journal Article
- From:Neurology Asia
2012;17(2):163-168
- CountryMalaysia
- Language:English
-
Abstract:
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare neurodegenerative
multisystem disorder inherited in an autosomal recessive manner and characterized clinically by
gastrointestinal dysmotility, cachexia, ophthalmoparesis and/or ptosis, peripheral neuropathy and
leukoencephalopathy. Heterogenous causative mutations in the thymidine phosphorylase (TP) gene
located on chromosome 22q13 have been identifi ed. This is the fi rst reported case of a 25-year-old
Malaysian patient, of indigenous Bajau ethnicity who presented with recurrent abdominal pain before
developing other clinical features of classical MNGIE. Biochemical correlates include elevated plasma
levels of thymidine, deoxyuridine and lactate. The brain MRI showed diffuse leucoencephalopathy
while nerve conduction studies were consistent with demyelinating polyneuropathy. Direct DNA
sequencing of the nine coding exons of the TP gene showed both a novel and a previously described
mutation. The former is a point mutation in exon 5 (NG_011860.1:g.7387C>T) at amino acid position
179, resulting in a stop codon and premature truncation of thymidine phosphorylase(TP) protein
while the latter mutation occurred at exon 10 (NG_011860.1:g.9279C>T) resulting in a missense
homozygous mutation at amino acid position 471. Defi nite diagnosis was based on clinical features,
plasma and urinary nucleosides and the identifi cation of mutations in the TP gene. This case report
adds to the knowledge of genotype-phenotype relationship of TP mutations and its occurrence among
ethnic groups worldwide.
- Full text:P020150710485318303793.pdf
