Case Report: Hyperinsulinemic hypoglycemia and arterial aneurysms in KAT6B-related disorder: case observation and...

KAT6B-related disorders (KAT6B-RD) are rare autosomal dominant chromatinopathies characterized by variable multisystem involvement and marked phenotypic heterogeneity.

We describe a preterm male infant with intrauterine growth restriction who developed recurrent hypoglycemia toward the end of the first week of life during parenteral nutrition weaning, requiring a glucose infusion rate of up to 12 mg/kg/min. Biochemical findings were consistent with hyperinsulinemic hypoglycemia, and glycemic control was rapidly achieved with diazoxide (initiated at 5 mg/kg/day and increased to 6.9 mg/kg/day). After treatment discontinuation at 4 months of age, he exhibited recurrent hypoglycemia again, requiring the resumption of diazoxide. The patient also exhibited complete scrotal agenesis with complex genital anomalies, agenesis of the corpus callosum, generalized hypotonia, severe feeding difficulties requiring gastrostomy, primary hypothyroidism, and aneurysmal dilation of the ascending aorta and proximal right coronary artery. Clinical exome sequencing identified a de novo heterozygous pathogenic KAT6B variant (c.3995del; p.Pro1332Leufs*2) in exon 17. Diazoxide was successfully discontinued at 12 months of age under continuous glucose monitoring.

This case highlights congenital hyperinsulinism and arterial aneurysms as a clinical association observed in a patient with KAT6B-RD. Rather than representing definitive novel features of the syndrome, these manifestations should be interpreted with caution as hypothesis-generating findings potentially linked to KAT6B-mediated epigenetic dysregulation, while accounting for potential perinatal confounding factors. These findings nonetheless support careful endocrine and cardiovascular surveillance and follow-up in patients with KAT6B-RD.