1.) Hereditary Thrombophilia (Blood Clotting Tendency) 遺傳性血栓體質（血液凝固傾向）

• Key Gene(s) 主要基因 : F5 (Leiden), F2, MTHFR, SERPINC1, PROC, PROS1

• Main Impact on Pregnancy and Maternal Health: Increases risk of venous thrombosis, miscarriage, pre-eclampsia, placental infarction, DVT/PE.

• 對懷孕及母體健康的主要影響 : 增加靜脈血栓、流產、子癲前症、胎盤梗塞及深層靜脈栓塞／肺栓塞（DVT/PE）風險。

2.) Preeclampsia / Gestational Hypertension 子癲前症／妊娠期高血壓

• FLT1, ENG, ACE, MTHFR, ACVR2A

• Endothelial dysfunction and abnormal placentation cause high blood pressure, placental insufficiency, IUGR.

• 內皮功能失常及胎盤異常導致高血壓、胎盤功能不足及胎兒宮內生長受限（IUGR）。

3.) Gestational Diabetes Susceptibility 妊娠糖尿病易感性

• TCF7L2, GCK, MTNR1B, SLC30A8, PPARG

• Causes hyperglycemia, excessive fetal growth, neonatal hypoglycemia, and increases long-term diabetes risk.

• 引致母體高血糖、胎兒過度生長、新生兒低血糖，並增加長期糖尿病風險。

4.) Recurrent Pregnancy Loss / Spontaneous Abortion Genes 反覆流產／自然流產相關基因

• F2, F5, NLRP7, KHDC3L, TUBB8, PLK4

• Genetic defects in implantation or early embryo development → recurrent miscarriages.

• 著床或早期胚胎發育的基因缺陷 → 導致反覆流產。

5.) Connective-Tissue and Vascular Fragility Disorders (Ehlers–Danlos, Marfan) 結締組織與血管脆弱疾病

• COL3A1, FBN1, TNXB, ELN

• Increases risk of uterine rupture, hemorrhage, poor wound healing, and pelvic organ prolapse.

• 增加子宮破裂、出血、傷口癒合不良及骨盆器官脫垂風險。

6.) Folate and Vitamin Metabolism Defects 葉酸及維他命代謝缺陷

• MTHFR, MTRR, VDR

• Impairs conversion of folate and vitamin D → higher neural-tube-defect risk, anemia, poor bone mineralization.

• 影響葉酸與維他命D轉化 → 增加胎兒神經管缺陷、貧血及骨質疏鬆風險。

7.) Inherited Hemoglobinopathies (α/β-Thalassemia, Sickle Cell) 遺傳性血紅蛋白病（α/β-地中海貧血、鐮刀型貧血）

• HBA1, HBA2, HBB, HBD

• Maternal anemia, fetal growth restriction, hydrops fetalis if both parents carriers.

• 導致母體貧血、胎兒生長受限；若父母皆為帶因者可引起胎兒水腫（hydrops fetalis）。

8.) Autoimmune and Immune-Regulation 自體免疫與免疫調節相關基因

• HLA-DRB1, PTPN22, STAT4, CTLA4

• Increases risk of lupus, antiphospholipid syndrome, inflammation, and placental failure.

• 增加紅斑狼瘡、抗磷脂症候群、發炎及胎盤功能衰退風險。

9.) Bleeding / Coagulation Factor Deficiency 出血／凝血因子缺乏症

• VWF, F8, F9, GP1BA

• Causes postpartum hemorrhage, poor surgical recovery, and anesthesia complications.

• 導致產後出血、手術恢復不良及麻醉併發症。

10.) Obesity, Lipid, and Metabolic Regulation Genes 肥胖、脂質與代謝調節基因

• FTO, LEPR, ADIPOQ, PPARG, MC4R

• Promotes excessive gestational weight gain, insulin resistance, and metabolic syndrome postpartum.

• 促進妊娠期過度體重增加、胰島素抗性及產後代謝症候群。

11.) Thyroid Function Variants 甲狀腺功能變異

• DUOX2, TG, TPO, TSHR

• Alters thyroid hormone synthesis → maternal hypo-/hyperthyroidism, miscarriage, or preterm birth.

• 改變甲狀腺激素合成 → 引致母體甲狀腺低／亢進、流產或早產。

12.) Polycystic Ovary Syndrome (PCOS) 多囊卵巢綜合症（PCOS）相關基因

• DENND1A, THADA, LHCGR, FSHR

• Irregular ovulation, infertility, higher risk of gestational diabetes and pre-eclampsia.

• 導致排卵不規則、不孕，並增加妊娠糖尿病及子癲前症風險。

13.) Bone, Calcium & Vitamin D Metabolism Disorders 骨骼、鈣及維他命D代謝異常

• VDR, CYP27B1, CALB1, COL1A1

• Leads to bone pain, low calcium, muscle cramps, poor fetal skeletal development.

• 導致骨痛、低血鈣、肌肉痙攣及胎兒骨骼發育不良。

14.) Iron & Anemia-Related Variants 鐵與貧血相關基因

• HFE, TMPRSS6, SLC40A1

• Reduced iron absorption → maternal anemia, fatigue, decreased oxygen supply to fetus.

• 降低鐵吸收 → 導致母體貧血、疲倦及胎兒供氧不足。

15.) Mitochondrial & Energy Metabolism Disorders (Carrier States) 粒線體與能量代謝疾病（帶因狀態）

• POLG, MT-ND1–ND5, ACADM, ETFA/B

• Affects cellular energy → fatigue, lactic acidosis, potential neonatal metabolic crisis.

• 影響細胞能量代謝 → 容易疲勞、乳酸中毒，嚴重可致新生兒代謝危機。

16.) Hormone and Neurotransmitter Regulation Genes (Mood & Stress) 荷爾蒙與神經傳導調控基因（情緒與壓力）

• COMT, SLC6A4, BDNF, OXTR

• Predisposes to prenatal anxiety or depression, affects maternal stress adaptation.

• 易出現孕期焦慮或抑鬱，影響母體壓力適應。

17.) Skin, Collagen & Elasticity Genes 荷爾蒙與神經傳導調控基因（情緒與壓力）

• COL1A1, MMP9, ELN, TGFB1

• Associated with stretch marks, varicose veins, poor tissue recovery after delivery.

• 與妊娠紋、靜脈曲張、皮膚恢復力差有關。

18.) Detoxification & Oxidative Stress Response Genes 皮膚、膠原與彈性基因

• GSTT1, GPX1, SOD2, NQO1

• Increases oxidative stress during pregnancy, contributing to inflammation and tissue aging.

• 懷孕期間氧化壓力增加，導致發炎及組織老化風險上升。

Clinical Significance

• Many inherited metabolic disorders detected through maternal carrier testing (with paternal carrier confirmation) are treatable if identified early, so early diagnosis is highly valuable.

• Early diagnosis allows doctors to adjust nutrition, monitoring, and newborn care, leading to better pregnancy management and improved outcomes for both mother and baby.

臨床意義

• 許多可經由母體帶因者篩查（並配合父體確認）發現的先天代謝疾病，只要及早診斷，其實是可以治療或有效控制的，因此早期檢測具有極高臨床價值。

• 透過及早發現，醫生可以調整孕期營養、監測計劃及新生兒照護方式，從而提升孕期管理成效，讓媽媽同BB都更安全、更健康。

嚴重嘅代謝病通常在初生嬰兒階段出現

• 常見症狀包括：BB唔肯食嘢、成日嘔、嗜睡、無力、手腳軟、抽筋、呼吸急促，甚至突然昏迷。

• 如果唔即刻發現同治療，可能會影響腦部發育、器官功能，甚至有生命危險。若發現BB有上述情況，應立即求醫並考慮進行檢測，以便早期診斷和治療。

• Early detection through WGS allows timely treatment — such as special diets, cofactors (e.g., biotin, riboflavin, carnitine), or enzyme replacement — before irreversible damage occurs.

• 透過全基因組檢測（WGS）早期發現，可以在未造成永久性損害前進行治療 — 例如採用特別飲食、補充輔助因子（如生物素、核黃素、肉鹼），或進行酶替代治療。

以下為這 10 大分類：

• Fatty Acid Oxidation Disorders 脂肪酸氧化異常疾病

• Organic Acidurias & Ketone Disorders 有機酸尿症與酮體代謝異常疾病

• Amino Acid & Urea Cycle Disorders 胺基酸及尿素循環異常疾病

• Carbohydrate & Energy Metabolism Disorders 碳水化合物與能量代謝異常疾病

• Mitochondrial & Peroxisomal Disorders 粒線體及過氧化體相關疾病

• Lysosomal Storage Disorders 溶小體儲積症

• Congenital Disorders of Glycosylation 先天性糖基化異常疾病

• Vitamin, Cofactor & Transport Deficiencies 維他命、輔因子及運輸缺陷疾病

• Cholesterol, Bile Acid & Sterol Disorders 膽固醇、膽汁酸及固醇代謝異常疾病

• Neuromuscular & Structural Disorders with Metabolic Basis 具代謝基礎的神經肌肉及結構性疾病