Development of a new diagnostic method and identification of new biomarkers for acid sphingomyelinase deficiency

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16882
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Akita University
• Principal Investigator: Kato Akie 秋田大学, 医学部附属病院, 医員 (90865718)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 酸性スフィンゴミエリナーゼ / 乾燥濾紙血 / タンデムマス / ライソゾーム病

Outline of Final Research Achievements

Acid sphingomyelinase deficiency (ASMD), a lysosomal disease, is one of the major targets of intractable disease care in Japan; ASMD is difficult to diagnose due to its rarity and symptom diversity; diagnosis is based on low ASM activity, but conventionally, one patient was measured over several months using cultured skin fibroblasts. In this study, we developed a novel diagnostic method based on tandem mass analysis using dried blood spot (DBS) and established a system that can be used for high-risk screening. Specifically, 176 patients could be measured within one drop of blood and two days.
Since enzyme replacement therapy for ASMD is ineffective for neurological symptoms, further pathophysiological clarification is needed; since only one ASMD patient was included in the study, the identification of a novel biomarker was not achieved, and this will be the next subject of research.

Free Research Field

小児代謝学、新生児学

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した診断法の特徴は、検査に伴う侵襲性を軽減したことと、ハイリスクスクリーニングに対応可能とした点である。これにより、ASMDの早期診断・早期治療に寄与することができる。
新診断法を確立したことに加え、2つの臨床研究を通じて、統計学的解析を行うことにより、DBS中ASM活性の様々な特徴を明らかにした。主に、①患者白血球数・リンパ球はASM活性と正の相関を示すため、軽症ASMD患者の偽陰性・保因者の偽陽性に関わる可能性があること、②新生児においてASM活性は在胎週数・出生体重と正の相関を示すこと、を明らかとした。これらは初めての報告であり、診断を進めていく上で貴重な基盤となった。