Clinical characteristics and influencing factors of children with MT-TL1 gene m.3243A>G mutation: a phenotypic study based on 11 han chinese patients

Fan Yang; Xiumin Wang

doi:10.1530/endoabs.110.P802

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Endocrine Abstracts (2025) 110 P802 | DOI: 10.1530/endoabs.110.P802

ECEESPE2025 Poster Presentations Multisystem Endocrine Disorders (43 abstracts)

Clinical characteristics and influencing factors of children with MT-TL1 gene m.3243A>G mutation: a phenotypic study based on 11 han chinese patients

Fan Yang ^1,2 & Xiumin Wang ³

Author affiliations

¹Department of Clinical Research Ward, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, shanghai, China; ²Shanghai Children’s Medical Center, Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Department of Endocrinology and Metabolism, shanghai, China; ³Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

JOINT306

Background: The MT-TL1 gene encodes mitochondrial tRNA ^{leu (UUR)}, playing a crucial role in mitochondrial protein synthesis. Mutations in this gene are associated with various mitochondrial diseases, often exhibiting clinical phenotypic heterogeneity. This study aims to retrospectively analyze 11 pediatric inpatients carrying the same MT-TL1 gene mutation to explore phenotypic variation and potential influencing factors.

Methods: We retrospectively analyzed 11 pediatric patients diagnosed with MT-TL1 gene mutations at our hospital between 2012 and 2024, along with their family histories. Clinical data were collected and analyzed, including demographics, age at diagnosis, clinical manifestations, imaging, and laboratory Results Phenotypic differences between the patients were systematically compared to evaluate the heterogeneity of the m.3243A>G mutation in children.

Results: Despite all 11 patients carrying the same MT-TL1 mutation, their clinical presentations varied significantly. The average diagnostic delay was 3.35 years. Neurological symptoms were present in 81.8% of the patients, 72.8% had endocrine issues, 18.2% had visual impairments, and 9.1% experienced bilateral hearing loss. Cardiac abnormalities were found in 63.6% of patients, 81.8% had gastrointestinal symptoms, 36.4% exhibited hypertrichosis, and 27.3% had used a ventilator. Plasma lactate levels were elevated in 90.1% of patients, with 80% exceeding 5 mmol/l. Additionally, 81.8% showed exercise intolerance and muscle weakness. Based on the diagnostic criteria, 45.5% were diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 18.2% were diagnosed with both MELAS and neuropathy, ataxia, and retinitis pigmentosa (NARP), and 54.5% were diagnosed with mitochondrial myopathy. Family history analysis revealed that three patients had relatives retrospectively diagnosed with mitochondrial myopathy, two were diagnosed with diabetes, and two with Kallmann syndrome.

Conclusion: This study highlights the clinical heterogeneity of the same MT-TL1 gene mutation in pediatric patients. Over 80% of the patients exhibited symptoms such as epilepsy, imaging abnormalities, short stature/malnutrition, gastrointestinal symptoms, elevated lactate levels, and muscle weakness. More than one-third of patients experienced stroke-like episodes, developmental delays, myocardial damage, elevated liver enzymes, abdominal pain, and hypertrichosis. Pediatric patients with these recurrent symptoms should be considered for m.3243A>G mutation screening.