Elevated beta-hydroxybutyrate within a pediatric population and its associated pathology: A retrospective case series

Elevated beta-hydroxybutyrate (BHB) is a marker for ketoacidosis. Post-mortem values for the diagnosis of fatal ketoacidosis and the associated clinical and histologic findings are limited in the pediatric population. A retrospective case series of pediatric autopsy records and histology slides was conducted. Deaths occurring between 2010 and 2022 of children (ages<18 years) with an elevated BHB level (vitreous BHB >2 mmol/L or blood >200 mg/L) were analyzed. Histology of the heart, lung, liver, and kidneys was reviewed and scored. Five hundred twelve pediatric autopsies were conducted during the study period, of which 20 cases (3.9%) met the inclusion criteria. The age ranged from stillborn to 17 years, with a mean age of 6.3 years and a median age of 3.5 years. The mean concentration of vitreous BHB was 3.9 mmol/L (median 2.69; range 2.0-11.86 mmol/L; n = 17 cases) and the blood BHB had a mean of 416 mg/L (median 291; range from <50 mg/L to 1188 mg/L; n = 9 cases). Death was attributed to diabetic ketoacidosis, infection, malignancy, trauma, congenital heart disease, and drug toxicity. Histological changes were seen in all tissues examined in this pediatric population including hepatic steatosis (n = 17), glycogenated hepatocyte nuclei (n = 5), renal tubular vacuoles (n = 7) and heart vacuoles (n = 9). The only statistically significant correlation was found between vitreous BHB and renal tubular vacuoles (p = 0.014). Overall, elevated BHB levels were identified in blood and/or vitreous in fatal diabetic and non-diabetic cases, including infection. Diabetic ketoacidosis had the highest level of BHB at 11.86 mmol/L.