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Background <p>Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem mitochondrial disorder caused by thymidine phosphorylase (TYMP) deficiency, leading to toxic nucleoside accumulation and mitochondrial DNA instability. Pathogenic variants in POLG, encoding mitochondrial DNA polymerase γ, have been associated with overlapping mitochondrial syndromes. However, the coexistence of TYMP-related MNGIE and a concurrent heterozygous POLG variant has not been reported.</p> Case presentation <p>A 57-year-old woman presented with a 10-year history of recurrent dizziness, chronic diarrhea, and 20&#xa0;kg weight loss. Laboratory investigations revealed chronic anemia, hypoproteinemia, and positivity for anti-centromere protein B and anti-mitochondrial M2 antibodies. Abdominal CT revealed multiple small-bowel diverticula, splenomegaly, and a retained capsule endoscope, whereas brain MRI showed diffuse white-matter hyperintensities. Electromyography showed sensorimotor neuropathy, and neurological examination revealed bilateral ptosis, ophthalmoplegia, and distal weakness. Whole-exome sequencing confirmed a homozygous TYMP variant (c.708C&gt;A, p.Phe236Leu) and a heterozygous POLG variant (c.1781&#xa0;T&gt;C, p.Leu594Pro). Surgical removal of the retained capsule together with supportive therapy, including enteral nutrition and coenzyme Q10, resulted in clinical improvement. To our knowledge, this is the first reported case of MNGIE with a homozygous TYMP variant and a concurrent heterozygous POLG variant.</p> Conclusion <p>While the homozygous TYMP variant provides the primary molecular basis for the diagnosis, the concurrent heterozygous POLG variant may represent a potential phenotypic modifier. This case expands the genotypic context of MNGIE and highlights the importance of early genetic testing and multidisciplinary management in patients with unexplained gastrointestinal and neurological manifestations.</p>

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MNGIE with TYMP and POLG variants presenting as decade-long capsule retention: A case report

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Yuan Xia,
  • Yufen She,
  • Ruiqi Zhao,
  • Yan Zhang

摘要

Background

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem mitochondrial disorder caused by thymidine phosphorylase (TYMP) deficiency, leading to toxic nucleoside accumulation and mitochondrial DNA instability. Pathogenic variants in POLG, encoding mitochondrial DNA polymerase γ, have been associated with overlapping mitochondrial syndromes. However, the coexistence of TYMP-related MNGIE and a concurrent heterozygous POLG variant has not been reported.

Case presentation

A 57-year-old woman presented with a 10-year history of recurrent dizziness, chronic diarrhea, and 20 kg weight loss. Laboratory investigations revealed chronic anemia, hypoproteinemia, and positivity for anti-centromere protein B and anti-mitochondrial M2 antibodies. Abdominal CT revealed multiple small-bowel diverticula, splenomegaly, and a retained capsule endoscope, whereas brain MRI showed diffuse white-matter hyperintensities. Electromyography showed sensorimotor neuropathy, and neurological examination revealed bilateral ptosis, ophthalmoplegia, and distal weakness. Whole-exome sequencing confirmed a homozygous TYMP variant (c.708C>A, p.Phe236Leu) and a heterozygous POLG variant (c.1781 T>C, p.Leu594Pro). Surgical removal of the retained capsule together with supportive therapy, including enteral nutrition and coenzyme Q10, resulted in clinical improvement. To our knowledge, this is the first reported case of MNGIE with a homozygous TYMP variant and a concurrent heterozygous POLG variant.

Conclusion

While the homozygous TYMP variant provides the primary molecular basis for the diagnosis, the concurrent heterozygous POLG variant may represent a potential phenotypic modifier. This case expands the genotypic context of MNGIE and highlights the importance of early genetic testing and multidisciplinary management in patients with unexplained gastrointestinal and neurological manifestations.