ESPE Abstracts

Background: Aminoacyl tRNA synthetases (ARSs) are enzymes that bind amino acids to tRNAs, and many of their genetic variants are known to be pathogenic. Asparaginyl Aminoacyl tRNA synthetase (NARS1) deficiency was first reported as a cause of microcephaly in 2020. NARS1 deficiency is characterized by microcephaly, psychomotor retardation, epilepsy, congenital abnormalities of the limbs and skeleton, and a peculiar facial appearance. However, there have been no reports of diabetes mellitus complicated with resulting from gradually progressive liver cirrhosis and pancreatic atrophy in patients with NARS1. We report a case of NARS1 deficiency with diabetes mellitus associated with liver cirrhosis and pancreatic atrophy.

Case Report: The patient was a 12-year-old Japanese boy born 37 weeks and one day after conception, weighing 1,884 g. He was treated with tube feeding due to poor weight gain. Liver dysfunction appeared at the age of one year. In addition, intrahepatic nodules, uncontrolled hypertriglyceridemia, hypoproteinemia, and intractable diarrhea were also observed since infancy. A liver biopsy was performed, but no neoplastic lesions were found. Although examination for inborn errors of metabolism was also performed, no abnormality was found. Liver damage progressed over time, and liver cirrhosis developed at school age. After Nissen surgery for gastroesophageal reflux at age four, hypoglycemia with insulin excess due to dumping syndrome was observed. It was difficult to control despite enteral nutritional support, oral diazoxide, and continuous subcutaneous octreotide injection, but we stopped octreotide injection due to severe gastrointestinal symptoms. Transient postprandial hyperglycemia associated with infection was observed from age seven and worsened over time, and his HbA1c increased to 7.5% at 12 years and pancreatic atrophy was found. His HbA1c quickly improved to normal after introducing insulin for postprandial hyperglycemia. Comprehensive genetic analysis identified a compound heterozygous mutation in NARS1, leading to the diagnosis of NARS1 deficiency.

Conclusion: This is the first report of NARS1 deficiency with liver cirrhosis and pancreatic atrophy resulting in diabetes mellitus.