2026-05-07 | Ultrasound assessment of diaphragmatic structure and function before and after orthotopic liver transplantation in MNGIE.

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder caused by thymidine phosphorylase (TP) deficiency, leading to systemic nucleoside accumulation and multisystemic dysfunction. While respiratory failure is not a primary feature, severe cachexia, sarcopenia, and respiratory muscle weakness may contribute to morbidity, particularly during acute illnesses. Orthotopic liver transplantation (OLT) has emerged as a disease-modifying therapy, restoring TP activity and normalizing circulating nucleosides, though its impact on respiratory muscle function remains largely unexplored. Diaphragmatic ultrasound offers a noninvasive tool to monitor respiratory muscle structure and function longitudinally. We report a 27 year-old male with genetically confirmed MNGIE who underwent OLT while severely cachectic (BMI 13.4 kg/m2). Pre-transplant diaphragmatic ultrasound demonstrated severe atrophy (thickness 1 mm) and dysfunction (thickening fraction < 10%). Seven years after OLT, diaphragmatic trophism and contractility had markedly improved (thickness 2.3 mm; thickening fraction 31%), whereas peripheral skeletal muscle recovery remained limited. During a subsequent septic episode, the patient required only brief mechanical ventilation, reflecting enhanced respiratory resilience. Orthotopic liver transplantation provides sustained metabolic correction in MNGIE, facilitating significant recovery of diaphragmatic structure and function, even in patients with advanced disease. Diaphragmatic ultrasound proved invaluable for the noninvasive assessment of respiratory muscle trophism and contractility, guiding ventilatory management and long-term follow-up. Importantly, this case demonstrates a dissociation between peripheral and diaphragmatic muscle recovery, suggesting differential responsiveness to post-transplant metabolic normalization. These results underscore the potential of diaphragmatic ultrasound as a sensitive functional biomarker in MNGIE, although larger studies are warranted to establish its prognostic and clinical relevance.

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2025-12-26 | Sequential development of three syndromes in a patient with m.3243A>G mutation: a case report.

Mitochondrial disorders are highly heterogeneous and can manifest as a spectrum of clinically heterogeneous disorders that affect multiple organ systems. Herein, we report a Chinese female patient carrying mitochondrial DNA m.3243A>G mutation who sequentially experienced myoclonic epilepsy with ragged red fibers, mitochondrial neurogastrointestinal encephalomyopathy, and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. This report expands the current understanding of phenotypic heterogeneity in mitochondrial disorders.

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2025-11-27 | Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE): A Comprehensive Review of Pathophysiology, Diagnosis, and Therapeutic Advances

Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) is a rare autosomal recessive multisystem disorder caused by mutations in the TYMP gene, leading to thymidine phosphorylase deficiency and subsequent mitochondrial DNA instability. This results in profound mitochondrial dysfunction primarily affecting the gastrointestinal and nervous systems. Clinically, MNGIE manifests as progressive gastrointestinal dysmotility, including chronic intestinal pseudo-obstruction, nausea, vomiting, diarrhea, and severe cachexia. Neurological features such as peripheral neuropathy, ophthalmoplegia, ptosis, and diffuse leukoencephalopathy further complicate the clinical picture. The disease typically presents in early adulthood but can manifest at any age, with significant variability in severity and progression. Diagnosis involves clinical evaluation, detection of elevated plasma thymidine and deoxyuridine, reduced thymidine phosphorylase activity, characteristic MRI findings, nerve conduction studies, and genetic testing for TYMP mutations. Therapeutic options remain limited but include allogeneic hematopoietic stem cell transplantation to restore enzymatic activity, experimental enzyme replacement therapies, gene therapy, and supportive care for symptom management. Early diagnosis and emerging molecular therapies offer hope for improved outcomes, although the prognosis remains poor due to the progressive and multisystem nature of the disease. This comprehensive review synthesizes current understanding of MNGIE’s pathophysiological mechanisms, diagnostic criteria, and recent advances in treatment strategies, highlighting challenges and future directions in managing this devastating disorder. DOI: https://doi.org/10.52783/jchr.v15.i6.10859

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