Clinical and molecular characterization of a patient with mitochondrial Neurogastrointestinal Encephalomyopathy

Abstract

Background Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by mutations in TYMP gene, encoding nuclear thymidine phosphorylase (TP). MNGIE mainly presents with gastrointestinal symptoms and is mostly misdiagnosed in many patients as malabsorption syndrome, inflammatory bowel disease, anorexia nervosa, and intestinal pseudo-obstruction. Up to date, more than 80 pathogenic and likely pathogenic mutations associated with the disease have been reported in patients from a wide range of ethnicities. The objective of this study was to investigate the underlying genetic abnormalities in a 25-year-old woman affected with MNGIE. Case presentation The patient was a 25-year-old female referred to our center with the chief complaint of severe abdominal pain and diarrhea for 2 years that had worsened from 2 months prior to admission. The clinical and para-clinical findings were in favor of mitochondrial neurogastrointestinal encephalomyopathy syndrome. Subsequent genetic studies revealed a novel, private, homozygous nonsense mutation in TYMP gene (c. 1013 C > A, p.S338X). Sanger sequencing confirmed the new mutation in the proband. Multiple sequence alignment showed high conservation of amino acids of this protein across different species. Conclusion The detected new nonsense mutation in the TYMP gene would be very important for genetic counseling and subsequent early diagnosis and initiation of proper therapy. This novel pathogenic variant would help us establish future genotype-phenotype correlations and identify different pathways related to this disorder.

Mitochondrial neurogastrointestinal encephalomyopathy in a Pakistani female: a case report

“…MNGIE is characterized by severe progressive gastrointestinal dysmotility, leukoencephalopathy, peripheral neuropathy, and ocular symptoms [ 1 ]. The symptoms generally start in the second or third decade of life (the average age at onset is 19 years) [ 7 ], whereas a sharp deterioration in survival is seen in the fourth decade of life [ 1 , 2 ]. Various treatment options have been proposed for MNGIE syndrome with variable success, including allogeneic hematopoietic stem cell transplant, gene therapy, enzyme replacement therapy, and orthotropic liver transplantation [ 8 ].…”

Rare pathogenic mutation in the thymidine phosphorylase gene (TYMP) causing mitochondrial neurogastrointestinal encephalomyelopathy

“…3 Currently, greater than 80 such mutations have been reported in patients from different ethnicities. 6 We report a 25-year-old patient with a novel homozygous variant of TYMP gene c.1048C>T. In 2020, the Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, Saudi Arabia, reported a novel mutation that was found in our patient to the National Institute of Health's genetic database. 7 However, in this manuscript, the authors described the same patient's detailed history, the clinical course of the disease, treatment, follow-up and the eventual decision to be enrolled in Dr. Hirano's ongoing clinical trial entitled, 'MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study (MASS)' (trial registration number: NCT02427178).…”

“… 3 Currently, greater than 80 such mutations have been reported in patients from different ethnicities. 6 …”

Gastrointestinal motility disorders in neurologic disease

“…The Journal of Clinical Investigation (150). Allogeneic stem cell transplantation (151) has been proposed as an early treatment for MNGIE while patients are still relatively healthy.…”