Urinary prostaglandin D2 and E2 metabolites are elevated with disease severity in patients with Fukuyama congenital muscular dystrophy.

Treatment approaches are lacking for Fukuyama congenital muscular dystrophy (FCMD), the second most common type of pediatric muscular dystrophy after Duchenne muscular dystrophy (DMD) in the Japanese population. Recent studies demonstrating the involvement of prostaglandin (PG) D2 in DMD progression has led to the development of novel inhibitors targeting hematopoietic PGD2 synthase. This study aimed to determine the role of PGD2 in FCMD etiology in 42 patients with FCMD and 77 healthy age-matched individuals. Concentrations of tetranor-PGDM and tetranor-PGEM, the metabolites of PGD2 and PGE2, respectively, and creatinine were measured in spot urine samples. Mean tetranor-PGDM/creatinine and tetranor-PGEM/creatinine concentrations and tetranor-PGEM/tetranor-PGDM ratio were significantly higher in patients with FCMD than the healthy controls (5.3 ± 2.1 and 30.9 ± 52.3 ng/mg creatinine and 6.8 ± 2.0 vs. 3.4 ± 0.3 and 9.5 ± 0.9 ng/mg creatinine and 3.2 ± 0.3, respectively; p = 0.0011, p < 0.0001 and p < 0.0001, respectively). These metabolites were increased in patients with typical and severe FCMD phenotypes than in those with the mild FCMD phenotype, indicating their correlation with disease severity. These results implicate that PGD2 and PGE2 play important roles in FCMD pathogenesis and that novel hematopoietic PGD2 synthase inhibitors and steroids used in DMD may also have therapeutic utility in FCMD.