Williams Robin A, Hooper Amanda J, Bell Damon A, Mamotte Cyril D S, Burnett John R
1Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth 2School of Medicine and Pharmacology, University of Western Australia, Perth 3School of Pathology and Laboratory Medicine, University of Western Australia, Perth 4Department of Internal Medicine, Royal Perth Hospital, Perth 5School of Biomedical Science and CHIRI Biosciences Research Precinct, Curtin University, Bentley, WA, Australia.
Pathology. 2015 Feb;47(2):134-7. doi: 10.1097/PAT.0000000000000210.
Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) catabolism resulting from a deficiency of L-phenylalanine hydroxylase (PAH). An association between hyperphenylalaninaemia (HPA) and hypocholesterolaemia has been reported in children. However, controversy exists as to whether this is due to the low protein diet or to a disruption to cholesterol biosynthesis inherent to those with PKU. We investigated the relationship between blood Phe and plasma cholesterol in 41 apparently healthy adults with PKU (26 female, 15 male, age 18-57 years, median age 26 years) attending a PKU outpatient clinic at an adult tertiary care hospital. Of these patients, 33 (80%) were compliant with a Phe-restricted diet with amino acid supplementation, whereas eight (20%) were not. The PKU subjects had a mean body mass index (BMI) of 30.3 ± 1.8 kg/m; 72% were obese, 14% overweight, with only 14% having normal BMI. The mean blood Phe was 1194 ± 522 μmol/L with plasma total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol and apolipoprotein (apo) B concentrations of 4.3 ± 0.8 mmol/L, 1.6 ± 0.8 mmol/L, 1.2 ± 0.3 mmol/L, 2.3 ± 0.8 mmol/L, and 0.83 ± 0.21 g/L, respectively. The mean LDL-cholesterol was 19% lower in PKU females than that of 8944 age-matched females from a community population (2.5 ± 0.8 mmol/L vs. 3.1 ± 0.9 mmol/L, p < 0.001). Similarly, the mean LDL-cholesterol was 32% lower in PKU males than 3786 age-matched males (2.1 ± 0.7 mmol/L vs. 3.1 ± 1.0 mmol/L, p < 0.0001). No correlations were observed between Phe and total cholesterol, LDL-cholesterol or apoB in the PKU cohort. Adults with PKU had low-normal cholesterol concentrations, with no correlation observed between Phe and cholesterol levels. Our findings support the concept that the HPA found in PKU, rather than an effect of a low-protein diet, leads to hypocholesterolaemia. Studies are required to determine whether this cholesterol-lowering effect confers cardioprotection.
苯丙酮尿症（PKU）是一种常染色体隐性疾病，因缺乏L - 苯丙氨酸羟化酶（PAH）导致苯丙氨酸（Phe）分解代谢紊乱。有报道称儿童中高苯丙氨酸血症（HPA）与低胆固醇血症有关。然而，对于这是由于低蛋白饮食还是PKU患者固有的胆固醇生物合成中断所致，仍存在争议。我们调查了41名在一家成人三级护理医院的PKU门诊就诊的表面健康的成年PKU患者（26名女性，15名男性，年龄18 - 57岁，中位年龄26岁）血液中Phe与血浆胆固醇之间的关系。这些患者中，33名（80%）遵循限制Phe饮食并补充氨基酸，而8名（20%）未遵循。PKU受试者的平均体重指数（BMI）为30.3±1.8kg/m²；72%肥胖，14%超重，只有14%的BMI正常。平均血液Phe为1194±522μmol/L，血浆总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和载脂蛋白（apo）B浓度分别为4.3±0.8mmol/L、1.6±0.8mmol/L、1.2±0.3mmol/L、2.3±0.8mmol/L和0.83±0.21g/L。PKU女性的平均低密度脂蛋白胆固醇比来自社区人群的8944名年龄匹配女性低19%（2.5±0.8mmol/L对3.1±0.9mmol/L，p<0.001）。同样，PKU男性的平均低密度脂蛋白胆固醇比3786名年龄匹配男性低32%（2.1±0.7mmol/L对3.1±1.0mmol/L，p<0.0001）。在PKU队列中，未观察到Phe与总胆固醇、低密度脂蛋白胆固醇或apoB之间的相关性。成年PKU患者的胆固醇浓度处于略低正常水平，未观察到Phe与胆固醇水平之间的相关性。我们的研究结果支持这样的概念，即PKU中发现的HPA而非低蛋白饮食的影响导致低胆固醇血症。需要进行研究以确定这种降胆固醇作用是否具有心脏保护作用。
