Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Royal Liverpool University Hospitals Trust, Liverpool L7 8XP, UK; Institute of Ageing and Chronic Disease, Musculoskeletal Biology, University of Liverpool, Liverpool L69 3GA, UK.
Department of Psychological Sciences, University of Liverpool, Liverpool L69 7ZA, UK.
Mol Genet Metab. 2018 Sep;125(1-2):135-143. doi: 10.1016/j.ymgme.2018.07.008. Epub 2018 Jul 19.
Concerns exist over hypertyrosinaemia that is observed following treatment with nitisinone. It has been suggested that tyrosine may compete with tryptophan for uptake into the central nervous system, and or inhibit tryptophan hydroxylase activity reducing serotonin production. At the National Alkaptonuria (AKU) Centre nitisinone is being used off-licence to treat AKU, and there is uncertainty over whether hypertyrosinaemia may alter mood. Herein results from clinical and biochemical assessments of depression in patients with AKU before and after treatment with nitisinone are presented.
63 patients were included pre-nitisinone treatment, of these 39 and 32 patients were followed up 12 and 24 months after treatment. All patients had Becks Depression Inventory-II (BDI-II) assessments (scores can range from 0 to 63, the higher the score the more severe the category of depression), and where possible urinary monoamine neurotransmitter metabolites and serum aromatic amino acids were measured as biochemical markers of depression.
Mean (±standard deviation) BDI-II scores pre-nitisinone, and after 12 and 24 months were 10.1(9.6); 9.8(10.0) and 10.5(9.9) (p ≥ 0.05, all visits). Paired scores (n = 32), showed a significant increase at 24 months compared to baseline 10.5(9.9) vs. 8.6 (7.8) (p = 0.03). Serum tyrosine increased at least 6-fold following nitisinone (p ≤ 0.0001, all visits), and urinary 3-methoxytyramine (3-MT) increased at 12 and 24 months (p ≤ 0.0001), and 5-hydroxyindole acetic acid (5-HIAA) decreased at 12 months (p = 0.03).
BDI-II scores were significantly higher following 24 months of nitisinone therapy in patients that were followed up, however the majority of these patients remained in the minimal category of depression. Serum tyrosine and urinary 3-MT increased significantly following treatment with nitisinone. In contrast urinary 5-HIAA did not decrease consistently over the same period studied. Together these findings suggest nitisinone does not cause depression despite some observed effects on monoamine neurotransmitter metabolism.
尼替西农治疗后观察到高酪氨酸血症，对此存在担忧。据推测，酪氨酸可能与色氨酸竞争进入中枢神经系统，或抑制色氨酸羟化酶活性，从而减少 5-羟色胺的产生。在全国尿黑酸尿症（AKU）中心，尼替西农正在被非处方用于治疗 AKU，对于高酪氨酸血症是否会改变情绪存在不确定性。本文报告了尼替西农治疗前后 AKU 患者的临床和生化评估结果。
63 例患者在尼替西农治疗前接受了评估，其中 39 例和 32 例患者在治疗后 12 个月和 24 个月进行了随访。所有患者均接受贝克抑郁量表 II （BDI-II）评估（评分范围为 0 至 63，得分越高，抑郁程度越严重），并在可能的情况下测量尿单胺神经递质代谢物和血清芳香族氨基酸，作为抑郁的生化标志物。
尼替西农治疗前、治疗后 12 个月和 24 个月的平均（±标准差）BDI-II 评分分别为 10.1（9.6）、9.8（10.0）和 10.5（9.9）（所有就诊均为 p≥0.05）。配对评分（n=32）显示，与基线相比，24 个月时显著增加 10.5（9.9）比 8.6（7.8）（p=0.03）。尼替西农治疗后，血清酪氨酸至少增加了 6 倍（所有就诊均为 p≤0.0001），尿 3-甲氧基酪胺（3-MT）在 12 个月和 24 个月时增加（p≤0.0001），而 5-羟吲哚乙酸（5-HIAA）在 12 个月时减少（p=0.03）。
在接受随访的患者中，尼替西农治疗 24 个月后 BDI-II 评分显著升高，但其中大多数患者仍处于轻度抑郁状态。尼替西农治疗后，血清酪氨酸和尿 3-MT 显著增加。相反，在同一研究期间，尿 5-HIAA 并没有持续下降。这些发现表明，尽管尼替西农对单胺神经递质代谢有一定影响，但不会导致抑郁。
