Retrospective analysis of 19 patients with 6-Pyruvoyl Tetrahydropterin Synthase Deficiency: Prolactin levels inversely correlate with growth.
Retrospective analysis of 19 patients with 6-Pyruvoyl Tetrahydropterin Synthase Deficiency: Prolactin levels inversely correlate with growth.
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DOI：
10.1016/j.ymgme.2020.11.004
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发表时间：
2020-12
影响因子：
3.8
通讯作者：
Longo N
中科院分区：
文献类型：
--
作者：
Manzoni F;Salvatici E;Burlina A;Andrews A;Pasquali M;Longo N
丙酮酰四氢蝶呤合成酶 (PTPS) 缺乏症是 BH4 缺乏症最常见的形式，可导致高苯丙氨酸血症。它的临床严重程度各不相同，并且有关该病症的临床表现、自然史和新生儿筛查有效性的信息有限。收集了不同中心 19 名 PTPS 缺乏症患者的回顾性数据（生长和临床参数、生化和基因检测结果、治疗），以评估生化和临床结果。描述性统计用于定性变量，而线性回归分析用于关联定量变量。 PTPS缺乏的患者早产发生率增加（4/18），平均胎龄仅轻度降低（37.8±2.4周）且出生体重低（-1.14±0.97 SD低于预测胎龄）。随着时间的推移，体重和身高逐渐接近正常。价值观。所有患者均通过新生儿筛查发现苯丙氨酸水平升高。然而，在 24 小时或之前进行测试的两名患者中，苯丙氨酸水平正常。沙丙蝶呤二盐酸盐治疗使苯丙氨酸水平正常化。分子测试发现了 PTS 基因的新变异，其中一些变异存在于多个受影响的家族中。除 2 个外周型 PTPS 缺乏的家系外，大多数病例脑脊液中的神经递质衍生物 5-羟基吲哚乙酸 (5HIAA) 和高香草酸 (HVA) 均减少。随着时间的推移，其中两名需要治疗的患者的 HVA 和 5HIAA 变得异常低。在一些 PTPS 缺乏的患者中，催乳素（其分泌受到多巴胺抑制）水平升高，并且与身高 (p<0.01) 和体重 (p<0.05) 的 z 得分呈负相关。大多数患有 PTPS 缺乏症的患者在生命早期发育迟缓，在学龄期左右有所改善，智商大多在正常范围内，老年人的智商略有下降。从神经学的角度来看，大多数患者的脑部 MRI 正常，脑电图轻微异常，尽管有些患者有持续的神经系统症状。 PTPS 缺乏的患者不仅早产发生率增加，而且在校正胎龄后出生体重也会下降。高苯丙氨酸血症在出生第一天可能不会出现。使用沙丙蝶呤二盐酸盐治疗可以使苯丙氨酸水平正常化，神经递质前体可以改善脑脊液神经递质代谢物水平。多巴胺能刺激不足（如催乳素升高所见）可能会导致 PTPS 缺乏症患者身高下降。尽管早期发育延迟，但许多患者可以在成年后实现独立生活，神经影像和脑电图通常正常。
Pyruvoyl Tetrahydropterin Synthase (PTPS) Deficiency is the most common form of BH4 deficiency resulting in hyperphenylalaninemia. It can have variable clinical severity and there is limited information on the clinical presentation, natural history and effectiveness of newborn screening for this condition. Retrospective data (growth and clinical parameters, biochemical and genetic testing results, treatment) were collected from 19 patients with PTPS deficiency in different centers, to evaluate biochemical and clinical outcomes. Descriptive statistics was used for qualitative variables, while linear regression analysis was used to correlate quantitative variables. Patients with PTPS deficiency had an increased incidence of prematurity (4/18) with an average gestational age only mildly reduced (37.8±2.4 weeks) and low birth weight (−1.14±0.97 SD below that predicted for gestational age). With time, weight and height approached normal. values. All patients were identified by newborn screening for an elevated phenylalanine level. However, phenylalanine levels were normal in two whose testing was performed at or before 24 h of age. Sapropterin dihydrochloride treatment normalized phenylalanine levels. Molecular testing identified novel variants in the PTS gene, some of which present in more than one affected family. The neurotransmitter derivatives 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in the CSF were decreased in most cases except in 2 families with the peripheral form of PTPS deficiency. With time, HVA and 5HIAA became abnormally low in two of these patients requiring therapy. Prolactin (whose secretion is inhibited by dopamine) levels were elevated in several patients with PTPS deficiency and inversely correlated with the z-scores for height (p<0.01) and weight (p<0.05). Most patients with PTPS deficiency had delayed development early in life, improving around school age with IQs mostly in the normal range, with a small decline in older individuals. From a neurological standpoint, most patients had normal brain MRI and minor EEG anomalies, although some had persistent neurological symptoms. Patients with PTPS deficiency have not only an increased incidence of prematurity, but also decreased birth weight when corrected for gestational age. Hyperphenylalaninemia can be absent in the first day of life. Therapy with sapropterin dihydrochloride normalizes phenylalanine levels and neurotransmitter precursors can improve CSF neurotransmitter metabolites levels. Insufficient dopaminergic stimulation (as seen from elevated prolactin) might result in decreased height in patients with PTPS deficiency. Despite early delays in development, many patients can achieve independence in adult life, with usually normal neuroimaging and EEG.
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影响因子：
5.1
作者：
DHONDT, JL
通讯作者：
DHONDT, JL
影响因子：
4.1
作者：
Manti, Filippo;Nardecchia, Francesca;Leuzzi, Vincenzo
通讯作者：
Leuzzi, Vincenzo
影响因子：
4.2
作者：
PONZONE, A;BLAU, N;ENDRES, W
通讯作者：
ENDRES, W
影响因子：
4.7
作者：
Madsen, JT;Jansen, P;Gramsbergen, JB
通讯作者：
Gramsbergen, JB
影响因子：
--
作者：
Chaiyasap P;Ittiwut C;Srichomthong C;Sangsin A;Suphapeetiporn K;Shotelersuk V
通讯作者：
Shotelersuk V