ESPE Abstracts (2018) 89 P-P2-072

Syndromic Patients with Negative Islet Autoantibodies should be Tested for Mongenic Diabetes: Lessons from Patient with Trmt10a Mutation

Zeynep Siklara, Kevin Colcloughb, Kashyap A Patelc, Tuğba Çetina & Merih Berberoğlua


aAnkara University School of Medicine Department of Pediatric Endocrinology, Ankara, Turkey; bMolecular Genetics Laboratory, Royal Devon and Exeter Hospital, Exeter, UK; cUniversity of Exeter Medical School, Exeter, UK


Aim: Glucose metabolism can affect by several genes, and some of them represent distictive clinical and laboratory features. tRNA methyltransferase 10 homologue A (TRMT10A) gene is a tRNA methyl transferase, and localised to the nucleolus, where tRNA modifications occur. Very recently, a novel syndrome of abnormal glucose homeostasis or nonautoimmune diabetes associated with microcephaly, epilepsy, intellectual disability, failure to thrive, delayed puberty caused by mutations in the TRMA10A were reported in four family.

Case report: The patient was the second child born to non-consanguineous parents. The child’s birth weight was 2100 g and she had microcephaly. She was found to have difficulty in feeding at the first two years of age, not getting enough weight, fasting hypoglcaemia and retarded of neuromotor development with mild intellectual disability (24 months walking, 36 months speech). Dysmorphic features were apparent from early age, including a small face and deeply located eyes. She was diagnosed with epilepsy at 2.5 years old and treated with phenobarbital. On the cranial imaging, a pituitary normal structure, but an anterior arachnoid cyst of the left temporal lobe 3.5×2 cm was detected. At 3.65 years of age, her height was S.D.S.: −3.26, weight was S.D.S.:−2.22, and bone age was 2 years and 6 months. Growth hormone stimulation tests approppriate with partial growth hormone deficiency. Growth velocity was low during follow-up, then at 5.47 years of age rhGH therapy was initiated. She had incidental diagnosis of diabetes at age 11.41 years. She no antibodies, had normal c-petpide level (1.29 ng/ml) and treated with Metformin. Pubertal delay and low basal and stimulated gonadotropins were detected at the age of 13 years, and the patient underwent estrogen replacement. Mutation of the TRMT10A NM_001134665.2:c.379C>T (p.Arg127*) was detected in the molecular study. At last examination, she is 14,25 years of age, and height: 142 cm (HSDS: −2.95), Weight: 29.4 kg, RBMI: 72%. With metformine therapy, blood glucose level were normal and HbA1c level was 6.8%.

Conclusion: TRMT10A mutation appears to cause a syndrome of intellectual disability, microcephaly and delayed puberty. These features are associated with an unusual form of impaired glucose metabolism presenting in early childhood with hypoglycemia and nonautoimmune insulinopenic diabetes becomes evident as in our patient. Arachnoid cyst, although not reported before, and hypophyseal dysfunction can be additional findings of this syndrome. Slow onset diabetes with antibody negative with extras pancreatic features should be tested for monogenic diabetes.

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