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J Pediatr Genet 2019; 08(01): 015-019
DOI: 10.1055/s-0038-1661411
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Mitochondrial Neurogastrointestinal Encephalomyopathy Disease in Three Siblings from Pakistan with a Novel Mutation

Sana Durrani
1   Aga Khan Medical College, Karachi, Pakistan
,
Bee Chin Chen
2   Unit of Biochemical Genetics, Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
,
Yusnita Yakob
3   Unit of Molecular Diagnostics and Protein, Institute for Medical Research, Kuala Lumpur, Malaysia
,
Lua Seok Hian
3   Unit of Molecular Diagnostics and Protein, Institute for Medical Research, Kuala Lumpur, Malaysia
,
Bushra Afroze
4   Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan
› Author Affiliations Funding None.
Further Information

Publication History

27 October 2017

24 May 2018

Publication Date:
30 June 2018 (online)

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Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem autosomal recessive disorder. The disease is clinically heterogeneous with gastrointestinal symptoms of intestinal dysmotility and cachexia as well as neurological symptoms of ophthalmoplegia, neuropathy, sensorineural hearing impairment, and diffuse leukoencephalopathy being most prominent. MNGIE is caused by mutations in TYMP, a gene that encodes thymidine phosphorylase (TP)—a cytosolic enzyme. Mutations in TYMP lead to very low TP catalytic activity, resulting in dramatically increased thymidine and deoxyuridine in plasma. We describe the clinical, biochemical, and neuroimaging findings of three boys with MNGIE from a Pakistani family with a novel homozygous mutation, c.798_801dupCGCG p. (Ala268Argfs*?), in exon 7 of TYMP.

Keywords

mitochondrial neurogastrointestinal encephalomyopathy - Pakistani patients - novel mutation - magnetic resonance imaging of brain - TYMP
 

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