Year of Publication



Public Health

Date Available


Degree Name

Master of Public Health (M.P.H.)

Committee Chair

Dr. Erin Haynes

Committee Member

Dr. David Toupin

Committee Member

Dr. Ketrell McWhorter


Aim: To obtain a better understanding of the non-ketotic hyperglycinemia (NKH) patient population in regards to clinical features, mortality, geographic clustering, genetics, and incidence rate within the University of Kentucky (UK) catchment area of Central and Eastern Kentucky.

Methods: Patients with ICD codes corresponding to NKH who were treated at UK between January 1, 2008, and July 1, 2022, and who had clinical documentation available for review were identified through UK’s medical records (N=15). Demographic and clinical data were obtained through review of these patient’s charts in the electronic medical record. Differences in features among patients was assessed utilizing Fisher Exact Test and ANOVA when appropriate. Incidence rate was calculated using live birth data provided by the Kentucky Cabinet for Health and Family Services.

Results: Statistically more neonatal onset patients were male (60%) compared to later onset periods (0%); however, the overall population was predominately female. Statistically more neonatal onset patients had excessive hiccups reported (60%) compared to later onset periods (0%). There were no other statistically significant differences between onset periods or between the GLDC and AMT mutated groups. Most common symptoms included: poor feeding (87% presented/ 100% lifetime development), hypotonia (67% presented/ 87% lifetime development), and seizures (60% presented/ 87% lifetime development). 100% of patients who lived past neonatal period developed developmental delay. 87% of NKH patients (80% of neonatal onset patients) were still living as of January 1, 2023. There were 9 patients that had genetic data available. 8/9 had mutations in the GLDC and 5/6 with specific mutational data available had the c.1166C>T variant corresponding to a A389V change. The observed incidence rate among UK’s catchment area between 2008 and 2022 was 2.1 per 100,000.

Discussion: While there were few major differences observed between onset periods or between the gene that was mutated; there were major trends worth commenting on. Our population has a markedly different mortality rate than the up to 50% mortality rate for neonatal onset periods reported in the literature. Lifetime development of major symptoms was similar to what is reported in literature; however, certain presenting symptoms were less common. The c.1166C>T mutation was prevalent in this population and is a known “milder” mutation with significant residual enzyme activity left which could partially explain the attenuated and less fatal presentation. The incidence of NKH between 2008 and 2022 within UK’s catchment area is higher than global estimates which range from 0.4 to 1.3 per 100,000 but is less than the population with the highest incidence, Northern Finland, with 8.3 per 100,000.

Available for download on Friday, April 25, 2025

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