Mass spectrometry analysis of 24-hour urinary metabolites performed throughout therapy for 2 patients with Ghosal hematodiaphyseal dysplasia syndrome. Measurements of the urinary prostaglandin metabolites PGEM, PGDM, and PGIM are shown in panels A (for patient 1) and B (for patient 2). (C) The urinary metabolite of thromboxane A2 (TXM, 11-dehydrothromboxane B2 [9α,15S-dihydroxy-11-oxothromba-5Z,13E-dien-1-oic acid]). No TXM signal was detected in the patients’ urine samples. Daily productions of TXM in adult and child healthy controls were 504 ± 1 and 107 ± 3 ng/d, respectively. The urinary levels of LTE₄ are shown in panels D for case 1 and E for case 2. The urinary levels of 5-HETE are in panels F for case 1 and G for case 2. In each plot, the bar represents a mean ± standard deviation, for 3 replicate measurements, with statistical analysis indicated by the bar above, performed by one-way ANOVA. Red bars show urinary metabolites that were measured off therapy. Green bars show the metabolite levels on COX1/2 inhibitor therapy. Urinary metabolites for a control subject, age-matched for each patient are shown by the blue bars. (H) The results of eicosanoid metabolite analysis from A-F are summarized in the schematic diagram of AA metabolism, showing the aberrant accumulation of PGDM, PGEM, PGIM, 5-HETE and LTE₄ in Ghosal hematodiaphyseal dysplasia syndrome (upward red arrows). In Ghosal hematodiaphyseal dysplasia syndrome, TBXAS1 is inactive (red line), preventing the conversion of PGH₂ to TXA₂ and downstream conversion to TXB₂ and TXM. (I) Inhibition of COX-1/2 by NSAIDs (yellow box). ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001.