重新審視海洋性貧血帶因者篩檢之標準

Abstract

背景與研究目的 海洋性貧血為台灣常見之體染色體隱性遺傳疾病，臨床上多以平均紅血球容積(MCV)與平均紅血球血紅素(MCH)作為初步篩檢指標。然而，部分輕度甲型（如: -α3.7、-α4.2、Hb Constant Spring）與乙型（如: CD26）帶因者，其血液學數值可能高於傳統臨界值(MCV >80 fL、MCH >27 pg)，導致帶因者被誤判為陰性。若帶因夫妻雙方皆未被檢出，則可能產下中度或重度海洋性貧血胎兒，造成嚴重臨床後果。本研究旨在重新評估現行臨界值設定的敏感度與特異性，探討更合適的篩檢門檻，以提升診斷效能與遺傳風險預防能力。 材料與方法 本研究為回溯性設計，分析自2000年至2024年間產前檢查之成人全血球檢驗與基因檢測數據，並依據基因型分為甲型與乙型海洋性貧血帶因者進行分析。篩檢條件設為多組MCV(80–84 fL)、MCH <27 pg，及其複合條件，並比較其篩檢效能，包括敏感度、特異性、陽性預測值與陰性預測值。 研究結果 甲型帶因者中，以SEA型α⁰缺失最常見，右端缺失型(-α3.7)、左端缺失型(-α4.2)與CS型則顯示紅血球數值接近或高於臨界值。乙型帶因者以IVS-II-654與CD41/42為主，CD26型亦觀察到部分數值偏高。結果顯示，將MCV臨界值提高至84 fL可顯著提升敏感度（達98%以上），但特異性相對下降。MCH ≤27 pg 則呈現穩定且平衡之篩檢效能。當採用「MCV ≤82 或 MCH ≤27」的條件時，敏感度可提升至99%以上，有效降低假陰性率。 討論 傳統MCV ≤80 fL作為單一篩檢門檻，可能無法涵蓋紅血球指標位於邊緣的帶因者，尤其為輕度或非缺失型變異者。MCH指標則展現更穩定的表現，不易受檢體狀況影響。複合條件雖降低部分特異性，但可大幅提升整體篩檢效益，對於提升臨床偵測潛在高風險帶因者具重要意義。 結論 建議台灣現行海洋性貧血之篩檢標準應調整，採用「MCH ≤27 pg 或 MCV ≤82 fL」作為初篩條件，更能兼顧高敏感度與實務可行性。此一策略有助於降低中重度患兒出生風險，並提升產前遺傳諮詢與疾病預防之整體準確性與品質。

Background and Objectives Thalassemia is a common autosomal recessive disorder in Taiwan. Current screening mainly relies on mean corpuscular volume (MCV) ≤80 fL and mean corpuscular hemoglobin (MCH) ≤27 pg. However, certain α-thalassemia genotypes (e.g., -α3.7, -α4.2, Hb Constant Spring) and β-thalassemia variants (e.g., CD26) may present values above these thresholds, leading to missed diagnoses. If both carriers are undetected, they may conceive a fetus with moderate or severe thalassemia. This study aimed to re-evaluate the current cutoffs and propose more effective screening criteria. Materials and Methods A retrospective analysis was conducted using adult prenatal CBC and genotyping data from 2000 to 2024. We assessed multiple MCV thresholds (80–84 fL), MCH <27 pg, and combined conditions to evaluate sensitivity, specificity, and predictive values. Results SEA type α⁰ deletion was most prevalent. Mild variants like -α3.7, -α4.2, and Hb CS type showed borderline or elevated MCV/MCH values, as did CD26 among β-thalassemia cases. Raising the MCV cutoff improved sensitivity (up to >98%) but reduced specificity. MCH ≤27 pg showed more stable performance. The combined criterion “MCV ≤82 fL or MCH ≤27 pg” achieved >99% sensitivity with fewer false negatives. Discussion The current MCV cutoff may miss carriers with mild mutations. MCH is a more reliable standalone marker. Combined screening improves detection, though with slightly reduced specificity, and is especially valuable in preventing high-risk pregnancies. Conclusion We recommend adopting “MCV ≤82 fL or MCH ≤27 pg” as the screening threshold in Taiwan to enhance sensitivity, reduce missed cases, and improve prenatal thalassemia prevention.