The biokinetics of the enzyme by a novel alpha-galactosidase gene mutation in Fabry disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kagoshima University
• Principal Investigator: Higuchi Koji 鹿児島大学, 医歯学域医学系, 助教 (90448580)
• Co-Investigator(Kenkyū-buntansha): 吉満 誠 鹿児島大学, 医歯学域医学系, 准教授 (70404530)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: ファブリー病

Outline of Final Research Achievements

In a case of Fabry disease with normal enzyme activity in plasma and decreased enzyme activity in leukocytes, the α-gal A gene mutation was a missense mutation. This mutation was overexpressed in HeLa cells using lentiviral vectors. α-gal A enzyme activity was increased in the culture supernatant, but not in the leukocytes or intracellular enzyme activity, reproducing the clinical event. In this mutation, the amino acid was substituted from neutral to acidic amino acid. When this amino acid substitution was replaced with a basic amino acid, the same event was not observed, but when the amino acid was replaced with an acidic amino acid, which is different from this mutation, the same phenomenon was confirmed.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

ファブリー病の原因となるαガラクトシダーゼ酵素活性の低下は、αガラクトシダーゼ酵素の遺伝的変異によっておこることが知られている。本症例で認められたαガラクトシダーゼ酵素の遺伝子変異では、血漿酵素活性は正常であるが、白血球中の酵素活性が低下していることが分かった。αガラクトシダーゼ酵素の生体内動態を解明することにより、この酵素活性の乖離が説明できれば、病態解明や新規治療法の開発につながることが予想される。