Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) in a Malaysian patient with a novel mutation in thymidine phosphorylase gene: A case report

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 identified. This is the first 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. Definite diagnosis was based on clinical features, plasma and urinary nucleosides and the identification 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.