Department of Neonatology, Children's Hospital, Eberhard-Karls-University, Tübingen, Germany.
Department of Neonatology, Children's Hospital, Eberhard-Karls-University, Tübingen, Germany.
Nutrition. 2021 Sep;89:111348. doi: 10.1016/j.nut.2021.111348. Epub 2021 May 24.
In cystic fibrosis (CF), 85% to 90% of patients develop exocrine pancreatic insufficiency. Despite enzyme substitution, low pancreatic phospholipase A2 (sPLaseA2-IB) activity causes fecal loss of bile phosphatidylcholine and choline deficiency. We report on a female patient who has CF and progressive hepatosteatosis from 4.5 y onward. At 22.3 y, the liver comprised 27% fat (2385 mL volume) and transaminases were strongly increased. Plasma choline was 1.9 µmol/L (normal: 8-12 mol/L). Supplementation with 3 × 1g/d choline chloride decreased liver fat and volume (3 mo: 8.2%; 1912 mL) and normalized transaminases. Plasma choline increased to only 5.6 µmol/L upon supplementation, with high trimethylamine oxide levels (12-35 µmol/L; normal: 3 ± 1 mol/L) proving intestinal microbial choline degradation. The patient was homozygous for rs12325817, a frequent single-nucleotide polymorphism in the PEMT gene, associated with severe hepatosteatosis in response to choline deficiency. Resolution of steatosis required 2 y (4.5% fat). Discontinuation/resumption of choline supplementation resulted in rapid relapse/resolution of steatosis, increased transaminases, and abdominal pain.
在囊性纤维化（CF）中，85%至 90%的患者会出现外分泌胰腺功能不全。尽管进行了酶替代治疗，但低胰腺磷脂酶 A2（sPLaseA2-IB）活性导致粪便中胆磷脂和胆碱丢失，引起胆碱缺乏。我们报告了一名女性患者，她患有 CF，并在 4.5 岁后出现进行性肝脂肪变性。在 22.3 岁时，肝脏脂肪含量为 27%（2385 毫升体积），转氨酶显著升高。血浆胆碱为 1.9µmol/L（正常范围：8-12µmol/L）。补充 3×1g/d 氯化胆碱可降低肝脏脂肪和体积（3 个月：8.2%；1912 毫升），并使转氨酶正常化。补充后，血浆胆碱仅增加到 5.6µmol/L，三甲基胺氧化物水平很高（12-35µmol/L；正常范围：3±1µmol/L），证明肠道微生物降解了胆碱。该患者携带 rs12325817 纯合子，这是 PEMT 基因中常见的单核苷酸多态性，与对胆碱缺乏的严重肝脂肪变性有关。脂肪变性的解决需要 2 年（脂肪含量 4.5%）。停止/恢复胆碱补充会导致脂肪变性迅速复发/解决、转氨酶升高和腹痛。
