Introduction
Recently, recessive mutation of tRNA methyltransferase 10 homologue A (TRMT10A) was reported in some families as the cause of a novel syndrome of abnormal glucose homeostasis with microcephaly, epilepsy and intellectual disability. In the present paper, we report a Chinese young patient with diabetes, intellectual deficiency and microcephaly as a result of a homozygous mutation in the TRMT10A gene.
Case report
The patient had been found to have hyperglycemia for a week. The random blood glucose was 13.3 mmol/L, and the patient had no polyphagia, polydipsia, polyuria, weight loss or other abnormal symptom. The patient was the first child born to non-consanguineous parents. The pregnancy was uneventful and the child was born by a full-term cesarean section due to amniotic fluid turbidity. The child’s birth weight was 2800 g, but the birth length and head circumference were not recorded. The developmental milestones were abnormal and the child gradually began to show mild intellectual disability. The child had a fever and convulsion and was diagnosed with a febrile seizure once in preschool period. The child’s head circumference was 46 cm (−2.5 SD) in preschool period, while the height was 100 cm (−1.5 SD). At the time of diagnosis, the head circumference was 50 cm; the height was 143 cm (−3 SD); and the body mass index (BMI) was 15.65 kg/m2. There was no special appearance and acanthosis nigricans was absent. Glycated hemoglobin (HbA1c) was 14.4%, and all five pancreatic autoantibodies were negative. Oral glucose tolerance test (OGTT) showed a plasma glucose of 9 mmol/L at 0 min, and 23 mmol/L at 120 min, which confirmed the diagnosis of diabetes. Insulin and C-peptide levels indicated that the pancreatic β-cell function was well preserved (figure 1). No other abnormality was found in laboratory tests or imaging tests, including liver and kidney functions, thyroid function, electroencephalogram (EEG) and head MRI. In addition, intelligence testing indicated intellectual deficiency, with an IQ of 47.
The patient’s parents had normal heights, head circumferences and BMI, no epilepsy, no intellectual disability, no diabetes or pre-diabetes (normal OGTT results) and negative pancreatic autoantibodies, as well as the patient’s sibling, with normal birth history, normal growth and development history.
Genetic studies
Since the patient’s only manifestation is isolated and mild hyperglycemia, which does not meet the criteria for either type 1 diabetes or type 2 diabetes, it was suspected that the patient had monogenic diabetes. Exome sequencing, focusing on known diabetes genes, found a homozygous G to A transition in intron 5 of TRMT10A (NM_152292.4: c.496–1G>A), verified by Sanger sequencing. It was homozygous in the proband and heterozygous in both the patient’s parents and sibling (figure 2). Mutations of other monogenic diabetes genes were not detected.
Continuous glucose monitoring (CGM)
In the subsequent visit 3 months after diagnosis, the patient’s HbA1c decreased to 6.8% with the treatment of metformin, and the patient received the CGM for nearly 72 hours (figure 3). Since hypoglycemia has also been reported in this syndrome, we examined the patient’s daily glucose profile by CGM, which showed that the blood glucose was maintained at a stable level, with only one blood glucose value of less than 3.9 mmol/L. The average percent time on target (3.9–7.8 mmol/L) (figure 4) was 47%.