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

Sana Durrani; Bee Chin Chen; Yusnita Yakob; Lua Seok Hian; Bushra Afroze

doi:10.1055/s-0038-1661411

Journal of Pediatric Genetics, Table of Contents

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

Authors

Sana Durrani

¹Aga Khan Medical College, Karachi, Pakistan
Bee Chin Chen

²Unit of Biochemical Genetics, Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
Yusnita Yakob

³Unit of Molecular Diagnostics and Protein, Institute for Medical Research, Kuala Lumpur, Malaysia
Lua Seok Hian

³Unit of Molecular Diagnostics and Protein, Institute for Medical Research, Kuala Lumpur, Malaysia
Bushra Afroze

⁴Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan

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

Full Text

References

References
1 Hirano M, Lagier-Tourenne C, Valentino ML, Martí R, Nishigaki Y. Thymidine phosphorylase mutations cause instability of mitochondrial DNA. Gene 2005; 354: 152-156
2 Garone C, Tadesse S, Hirano M. Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. Brain 2011; 134 (Pt 11): 3326-3332
3 Martí R, Spinazzola A, Tadesse S, Nishino I, Nishigaki Y, Hirano M. Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays. Clin Chem 2004; 50 (01) 120-124
4 Cardaioli E, Da Pozzo P, Malfatti E. , et al. A second MNGIE patient without typical mitochondrial skeletal muscle involvement. Neurol Sci 2010; 31 (04) 491-494
5 Shaibani A, Shchelochkov OA, Zhang S. , et al. Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch Neurol 2009; 66 (08) 1028-1032
6 Tang S, Dimberg EL, Milone M, Wong LJ. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)-like phenotype: an expanded clinical spectrum of POLG1 mutations. J Neurol 2012; 259 (05) 862-868
7 Okamura K, Santa T, Nagae K, Omae T. Congenital oculoskeletal myopathy with abnormal muscle and liver mitochondria. J Neurol Sci 1976; 27 (01) 79-91
8 Nakhro K, Chung KW, Kim SM. , et al. Compound mutations of PEO1 and TYMP in a progressive external ophthalmoplegia patient with incomplete mitochondrial neurogastrointestinal encephalomyopathy phenotype. Genes Genomics 2011; 33: 431-437
9 Halter J, Schüpbach W, Casali C. , et al. Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant 2011; 46 (03) 330-337
10 Yavuz H, Ozel A, Christensen M. , et al. Treatment of mitochondrial neurogastrointestinal encephalomyopathy with dialysis. Arch Neurol 2007; 64 (03) 435-438
11 Cardaioli E, Sicurelli F, Carluccio MA. , et al. A new thymidine phosphorylase mutation causing elongation of the protein underlies mitochondrial neurogastrointestinal encephalomyopathy. J Neurol 2012; 259 (01) 172-174