RESUMEN
Thanatological biochemistry has gained prominence in determining causes of death, especially when suspected fatal pathologies do not exhibit clear postmortem macroscopic and/or microscopic features, such as in cases of ketoacidosis. Indeed, in these cases, the measurement of ß-hydroxybutyrate (BHB) in femoral blood and/or vitreous humor is of particular importance. However, data on its in vitro stability remain scarce, especially in vitreous humor. In this context, the study reported here aims to assess the in vitro stability of BHB. BHB quantification was performed using a liquid chromatography coupled with tandem mass spectrometry method. To investigate BHB stability, two different postmortem matrices were considered: femoral blood and vitreous humor. These matrices were pooled, aliquoted and spiked with BHB at three different concentrations (50 mg/L, 100 mg/L, and 200 mg/L; n = 3). Initial BHB concentrations were established on day 1. Each sample was then divided into two aliquots for storage under two conditions: 20 °C and 4 °C. Analyses were performed on Day 3, 7, 14, and 28. The study revealed no significant degradation of BHB in femoral blood or vitreous humor over time (days 1-28), confirming the robustness and reliability of BHB measurement in these matrices as a postmortem biomarker of ketoacidosis under the tested temperature conditions (+4 °C or -20 °C). These results support a systematic integration of BHB measurement into the routine workflow of forensic toxicology laboratories.
RESUMEN
BACKGROUND: Prescribing tramadol in children raises safety concerns. In Europe, tramadol is still approved and licensed for use in children over 1-3 years of age, depending on the country. In this context, the authors report a case of a tramadol overdose in a 5-year-old-child with a medical history of homozygous sickle cell disease. METHODS: Tramadol and M1 were quantified using liquid chromatography with a diode array detection method. CYP2D6 genotype was determined using a next generation sequencing platform (MISeq, Illumina). RESULTS: Tramadol and M1 were quantified in blood respectively at 5.48 and 1.32µg/mL at admission, at 0.77 and 0.35µg/mL 12hours later, and at 0.32 and 0.18µg/mL 20hours later. The patient was predicted as a CYP2D6 normal metabolizer (*35/*29). CONCLUSION: One of the most important difficulties with the use of tramadol in children relates to its pharmacokinetic (PK) properties. Indeed, tramadol's PK is characterized by a great variability related to: (i) anatomical/physiological factors that impact the volume of distribution (Vd); (ii) CYP2D6 genetic polymorphisms. Considering such an issue is particularly relevant to prevent poisoning. In the reported case, the plasma elimination half-life was estimated at 6.3h, significantly more than those reported in 2-8 year-old children (about 3h). This discrepancy does not seem related to genetic polymorphisms but rather to the Vd. Indeed, the patient was predicted to be a CYP2D6 normal metabolizer (*35/*29). The case presented here highlights the risk associated with the tramadol use in children and emphasizes the importance of considering PK variability among this population. Such variability necessitates greater caution in prescribing tramadol in children and highlights the importance of therapeutic education for families of children treated with this painkiller.
RESUMEN
Argininosuccinate lyase deficiency (ASLD, MIM #207900) is an inherited urea cycle disorder. There are mainly two clinical forms, an acute neonatal form which manifests as life-threatening hyperammonemia, and a late-onset form characterised by polymorphic neuro-cognitive or psychiatric presentation with transient hyperammonemia episodes. Here, we report a late-onset case of ASLD in a 72-year-old man carrying a homozygous pathogenic variant in the exon 16 of the ASL gene, presenting for the first time with fatal hyperammonemic coma. This case report shows the need to systematically carry out an ammonia assay when faced with an unexplained coma.