Congenital hyperinsulinism as part of a multisystem disease caused by a compound heterozygous variant in the <i>YARS1</i> gene.
This case illustrates that severe hyperinsulinemic hypoglycemia in infants with YARS1 variants may not respond to typical treatments like diazoxide and octreotide.
Where it sits
this study against the rest of the octreotide corpusSummary and findings
An infant with a compound heterozygous YARS1 genotype presented with severe hyperinsulinemic hypoglycemia. The patient showed a discordance between insulin and C-peptide concentrations and did not respond to diazoxide and octreotide. This case highlights the complexity of hypoglycemia in IMNEPD2.
Abstract
Tyrosyl-transfer RNA (tRNA) synthetase, encoded by <i>YARS1</i>, is essential for protein synthesis, catalyzing the attachment of tyrosine to its cognate tRNA during translation. Pathogenic biallelic <i>YARS1</i> variants cause infantile-onset multisystem neurological, endocrine, and pancreatic disease type 2 (IMNEPD2; OMIM #619418), an orphan disorder. Hypoglycemia in IMNEPD2 remains poorly characterized, with few reported cases. We describe an infant with a compound heterozygous <i>YARS1</i> genotype (c.176T>C and c.1261G>A) who presented with severe hyperinsulinemic hypoglycemia, notable for a discordance between insulin and C-peptide concentrations and a lack of response to diazoxide and octreotide.
Background
This paper addresses the genetic basis of congenital hyperinsulinism associated with YARS1 variants, which is linked to infantile-onset multisystem neurological, endocrine, and pancreatic disease type 2 (IMNEPD2). Prior knowledge on hypoglycemia in this disorder is limited, with few cases documented. Understanding the mechanisms behind hypoglycemia in IMNEPD2 is critical for better management and diagnosis.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
The findings highlight the complexity of hyperinsulinemic hypoglycemia in the context of YARS1 variants, suggesting that standard treatments like diazoxide and octreotide may not be effective. This case adds to the limited literature on IMNEPD2 and indicates that the clinical presentation can vary significantly. The lack of response to common treatments raises questions about the underlying mechanisms of hypoglycemia in this genetic context.
Key findings
- Compound heterozygous YARS1 genotype (c.176T>C and c.1261G>A) identified.
- Severe hyperinsulinemic hypoglycemia observed.
- Discordance between insulin and C-peptide concentrations noted.
- Lack of response to diazoxide and octreotide reported.
Limitations
- Single case report limits generalizability.
- Lack of detailed methodology.
- No quantitative results provided.