Normalization of dendritic spine numbers in rat hippocampus after termination of phenylacetate injections (PKU model)

Increased numbers of apical dendritic spines are present on hippocampal CA1 pyramidal cells in rats injected with phenylacetate from 2 to 21 days of life if animals are sacrificed at 20-30 days. However, if sacrificed at 60-90 days, spine counts are not significantly different from saline injected controls. These results suggest that this increased spine density at 3-4 weeks represents retardation of normal maturational spine loss rather than an actual hyperplasia, and is reversible upon termination of the phenylacetate injections. Implications for human pathologic series of phenylketonuria are discussed.     

苯丙酮尿症12例诊治体会及随访

本文总结了苯丙酮尿症（PKU）12例的主要临床表现，指出诊断该病应注意病史，初生良好，3－5个月起病，多有智能减退、婴儿痉挛症、运动落后、进行性加重、体征均有头发皮肤色素减退，体臭尿臭，EEC以高峰节律紊乱最多，其次为高幅慢节律，头颅CT多数正常，强调早期治疗，严格控制饮食中苯丙氨酸含量，控制癫痫发作，适当应用脑细胞活化剂，治疗晚者留下智能低下较普遍。     

“PKU Bodies”: Characteristic inclusions in the brain in phenylketonuria

Summary The ultrastructure of various inclusions within oligodendroglial cells in the brains from two phenylketonuric patients was studied. Characteristic lamellar, oval, slightly irregular inclusions measured between 0.5 and 2 micra in diameter and were bounded by a single membrane. The longitudinal and transverse lamellae of these inclusions had a distinct pattern. In analogy to lamellated but different inclusions of other diseases, these structures were termed PKU bodies. Various possibilities that would explain the morphogenesis of the PKU bodies and other inclusions in the oligodendroglial cells, and the significance of these findings, are discussed.     

Executive Function in School-Aged Children with Phenylketonuria

The hypothesis that, by school age, children with early-treated phenylketonuria (PKU) have specific cognitive deficits in executive function skills was examined in 19 children with PKU and 19 age-, sex-, and IQ-matched control participants. Five tasks were used, three chosen to measure executive, or frontal-lobe, functions (problem-solving, working memory, and verbal fluency) and two as control measures (verbal memory and spatial perception). Children with PKU performed more poorly on the problem-solving task and on the verbal memory task, suggesting that cognitive impairments associated with PKU persist into the school-age years. In addition, cognitive performance among the children with PKU was found to be specific to the phenylalanine (phe) levels at the time of testing. The high-phe group performed consistently more poorly than the control group on four of the six measures of the problem-solving task and on the verbal memory task, whereas the low-phe group was comparable to the control group on all measures.     

上海部分地区新生儿苯丙酮尿症筛查14年临床总结

从１９８１年１０月至１９９５年１２月，我室对在上海部分医院出生的６０万新生儿进行了苯丙酮尿症（ＰＫＵ）的筛查，共查出３５个阳性病例，发病率为１／１７１７８（３５／６０１２１８）。３３例确诊为经典型ＰＫＵ，另２例确诊为四氢生物喋呤缺乏症（ＢＨ＿４ｄｅｆｉｃｉｅｎｃｙ）．所有ＰＫＵ患者（除１例外）均在生后３２±１６天开始接受低苯丙氨酸奶方的治疗，取得了显著的疗效．在对本组ＰＫＵ患儿的随访中发现，绝大部分患儿２岁以前的血苯丙氨酸（ｐｈｅｎｙｌａｌａｎｉｎｅ，Ｐｈｅ）浓度控制在较理想的范围内（４－１０ｍｇ／ｄｌ），智商正常；２岁以后其血苯丙氨酸浓度常常超过１０ｍｇ／ｄｌ，智商明显下降。作者对比作了分析并就完善ＰＫＵ筛查阳性病例的临床管理作了初步探讨。     

早期筛查诊断治疗的45例苯丙酮尿症患儿智力发育分析

目的了解经新生儿疾病筛查确诊治疗的苯丙酮尿症（PKU）患儿的智力发育情况与其临床治疗依从性关系。方法自1999年-2009年经新生儿疾病筛查确诊的苯丙酮尿症患儿45名,选用0-6岁儿童神经心理发育量表评估患儿智力发育情况。结果 45例PKU患儿,除2例放弃治疗、1例死亡之外,治疗的42例患儿,有73.8%患儿智能发育达正常水平。生后40 d内即开始治疗的11例PKU患儿,和家长完全配合治疗的31例患儿,全部智能发育正常。完全配合治疗组、不配合治疗组患儿智力发育程度存在显著性差异。结论新生儿疾病筛查是早期发现PKU患儿的有效方法 ,患儿开始治疗时间的早晚及家长配合治疗程度直接影响患儿治疗效果。若患儿能在生后1个月内治疗,同时家长给予配合,可以避免智力低下的发生。     

Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria

Phenylketonuria (PKU) is a metabolic disorder, in which loss of phenylalanine hydroxylase activity results in neurotoxic levels of phenylalanine. We used the Pah^enu2/enu2 PKU mouse model in short- and long-term studies of enzyme substitution therapy with PEGylated phenylalanine ammonia lyase (PEG-PAL conjugates) from 4 different species. The most therapeutically effective PAL (Av, Anabaena variabilis) species was one without the highest specific activity, but with the highest stability; indicating the importance of protein stability in the development of effective protein therapeutics. A PEG-Av-p.C503S/p.C565S-PAL effectively lowered phenylalanine levels in both vascular space and brain tissue over a >90 day trial period, resulting in reduced manifestations associated with PKU, including reversal of PKU-associated hypopigmentation and enhanced animal health. Phenylalanine reduction occurred in a dose- and loading-dependent manner, and PEGylation reduced the neutralizing immune response to the enzyme. Human clinical trials with PEG-Av-p.C503S/p.C565S-PAL as a treatment for PKU are underway.     

Phenylketonuric diet negatively impacts on butyrate production

Background and aims

Phenylalanine (Phe) restricted diet, combined with Phe-free l-amino acid supplementation, is the mainstay of treatment for phenylketonuria (PKU). Being the diet a key factor modulating gut microbiota composition, the aim of the present paper was to compare dietary intakes, gut microbiota biodiversity and short chain fatty acids (SCFAs) production in children with PKU, on low-Phe diet, and in children with mild hyperphenylalaninemia (MHP), on unrestricted diet.

PKU导致智力落后儿童的训练个案分析

苯丙酮尿症（PKU）患儿1例,男,第1胎,足月,剖腹时有缺氧史,8个月时诊断为脑瘫,后查出PKU,血值不能控制在正常范围,患儿入院时采用儿童神经心理发展诊断量表和社会适应能力量表评定,其运动领域中双脚协调运动、平衡运动、感知能力、认知能力、语言能力、生活自理均为0分;社会适应领域中除认识家庭成员和认识自己评为2分和1分外,