A-267 Pediatric Neuropsychology Genetic Consultation: Rare de novo GCK Mutation with Severe Persistent Congenital Hyperinsulinemia (CH/CHI)

Abstract

Abstract Objective: Chromosomal abnormalities may result in neurodevelopmental delay. Mutations in the gene encoding the enzyme glucokinase (GCK) have been shown to result in congenital hyperinsulinemia (CH/CHI) and hyperglycemia (Galcheva et al., 2019). GCK is important for both glucose metabolism and homeostasis (Kraslow et al., 2021). Methods: The present case involves a 5-year-old, right-handed, Caucasian male, with a history of chromosomal abnormalities. DNA sequence analysis performed by PCR amplification of highly purified genomic DNA, followed by automated bi-directional DNA sequencing of coding regions of the genes revealed: GCK Variant 1: Transition T>C; Nucleotide position: 295; Codon position: 99; Amino acid change: Tryptophan>Arginine; DNA variant type: Disease-associated mutation, heterozygous; Inheritance: Autosomal Dominant; and Phenotype: CH. The patient had a history of severe persistent CH/CHI, obstructive sleep apnea, congenital chordee, cholelithiasis, and gross motor delay. He was referred for neuropsychological testing to ascertain the extent of his neurodevelopmental issues. Results: Neuropsychological testing revealed a diagnosis of a neurodevelopmental disorder characterized by an attention-deficit/hyperactivity disorder—combined type, dysexecutive syndrome/executive functioning disorder, below average general intellectual functioning and retention of new information, and severe behavioral dysregulation. Conclusion: Rare de novo GCK mutations with severe persistent CH/CHI are uncommon (Kraslow et al., 2021). According to Roper et al. (2020), roughly up to 48% of neonates affected with CH/CHI may exhibit sequelae of neurodevelopmental delay and intellectual disabilities. Analyses of GCK mutations and resultant neuropsychological deficits are rarely reported. Our case highlights the importance of pediatric neuropsychology genetic consultation in elucidating neurodevelopmental sequelae and academic and rehabilitation recommendations.