JIMD Reports, Volume 41

Hiroshi Kobayashi, Masamichi Ariga, Yohei Sato, Masako Fujiwara, Nei Fukasawa, Takahiro Fukuda, Hiroyuki Takahashi, Masahiro Ikegami, Motomichi Kosuga, Torayuki Okuyama, Yoshikatsu Eto, Hiroyuki Ida, Kobayashi, Hiroshi, Ariga, Masamichi, Sato, Yohei, Fujiwara, Masako, Fukasawa, Nei, Fukuda, Takahiro, Takahashi, Hiroyuki, Ikegami, Masahiro, Kosuga, Motomichi, Okuyama, Torayuki, Eto, Yoshikatsu, Ida, Hiroyuki

We report an autopsy case of a woman with mucopolysaccharidosis type I (MPS I) Hurler-Scheie syndrome who was treated with enzyme replacement therapy (ERT) for 12 years. This was the first case of MPS I treated with ERT in Japan. Pathological analysis showed no glycosaminoglycan accumulation in the liver and spleen as a result of long-term ERT, although severe aortic stenosis, diffuse intimal hyperplasia of the coronary artery, and fibrous hypertrophy of the endocardium were observed. Additionally, we detected subunit c mitochondrial ATP synthase (SCMAS) accumulation and mild tauopathy (hyperphosphorylated tau or p-tau, both 3-repeat and 4-repeat tau accumulation) in the same area of the cerebral limbic system and central gray matter of the mid brain and pons. Tauopathy is an important pathological finding in Alzheimer's disease and other neurodegenerative disorders; however, in MPS I, it is unclear whether tauopathy is a primary or secondary phenomenon. Thus, in this report, we describe pathological accumulation of p-tau and SCMAS in the context of MPS I and discuss the mechanisms and importance of these findings in the pathogenesis of MPS I.