A Novel Case of Mitochondrial Neurogastrointestinal Encephalopathy with Growth Hormone Deficiency: A Case Report

Background: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultrarare autosomal recessive metabolic disorder caused by mutations in the TYMP gene. The reported endocrine manifestations include diabetes, hyperlipidemia, and hypertriglyceridemia. However, growth hormone deficiency has not been previously described in the literature. Case presentation: This case describes a 19-year-old male with genetically confirmed MNGIE who presented with severe malnutrition (BMI 10.9 kg/m²) requiring total parenteral nutrition (TPN). Initially, he was developing normally, then the patient began experiencing chronic abdominal pain, vomiting, and diarrhea at age 11, along with noticeable short stature. Despite normal insulin-like growth factor 1 (IGF-1) levels, growth hormone deficiency was diagnosed through suboptimal responses to glucagon and clonidine stimulation tests. At age 13, he underwent duodenojejunostomy for superior mesenteric artery (SMA) syndrome, but symptoms persisted. Diagnostic workup, including endoscopy, imaging, and serological tests, excluded inflammatory bowel disease and celiac disease. Genetic testing confirmed a homozygous pathogenic mutation in the TYMP gene (p.Gly145Arg). Brain MRI revealed leukoencephalopathy with T2 and FLAIR hyperintensities in the centrum semiovale and parietal regions, which was consistent with MNGIE. Despite TPN therapy, the patient’s condition continues to progress, highlighting the need for early diagnosis and multidisciplinary management in MNGIE. Conclusion: This case highlights a novel presentation of growth hormone deficiency in MNGIE, offering new insights into its endocrine involvement. Despite treatment with somatotropin and TPN, patients’ nutritional improvement has remained limited, underscoring the need for more targeted therapies. Future research should focus on the link between mitochondrial dysfunction and endocrine abnormalities in MNGIE.