Niederwieser A, Blau N, Wang M, Joller P, Atarés M, Cardesa-Garcia J
Eur J Pediatr. 1984 Feb;141(4):208-14. doi: 10.1007/BF00572762.
A 4-year-old patient is described with hyperphenylalaninemia, severe retardation in development, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infections. Urinary excretion of neopterin, biopterin, pterin, isoxanthopterin, dopamine, and serotonin was very low, although the relative proportions of pterins were normal. In lumbar cerebrospinal fluid, homovanillic acid, 5-hydroxyindoleacetic acid, neopterin and biopterin were low. Oral administration of L-erythro tetrahydrobiopterin normalized the elevated serum phenylalanine within 4 h, serum tyrosine was increased briefly and serum alanine and glutamic acid for a longer time. Urinary dopamine and serotonin excretion were also increased. Administration of an equivalent dose of D-erythro tetrahydroneopterin was ineffective and demonstrated that this compound is not a cofactor in vivo and cannot be transformed into an active cofactor. GTP cyclohydrolase I activity was not detectable in liver biopsies from the patient. The presence of an endogenous inhibitor in the patient's liver was excluded. This is the first case of a new variant of hyperphenylalaninemia in which the formation of dihydroneopterin triphosphate and its pterin metabolites in liver is markedly diminished. Normal activities of xanthine oxidase and sulfite oxidase were apparent since uric acid levels were normal and no increase in hypoxanthine, xanthine, and S-sulfocysteine concentrations could be observed in urine. It is concluded that the molybdenum cofactor of these enzymes may not be derived from dihydroneopterin triphosphate in man. Also, since no gross abnormalities in the patient's immune system could be found, it seems unlikely that dihydroneopterin triphosphate metabolites, such as neopterin, participate actively in immunological processes, as postulated by others. See Note added in proof.
描述了一名4岁患者，患有高苯丙氨酸血症、严重发育迟缓、躯干严重肌肉张力减退和四肢张力亢进、惊厥以及无感染情况下频繁出现的高热发作。新蝶呤、生物蝶呤、蝶呤、异黄蝶呤、多巴胺和5-羟色胺的尿排泄量非常低，尽管蝶呤的相对比例正常。在腰椎脑脊液中，高香草酸、5-羟吲哚乙酸、新蝶呤和生物蝶呤含量较低。口服L-赤藓型四氢生物蝶呤在4小时内使升高的血清苯丙氨酸恢复正常，血清酪氨酸短暂升高，血清丙氨酸和谷氨酸升高时间更长。尿多巴胺和5-羟色胺排泄量也增加。给予等量的D-赤藓型四氢新蝶呤无效，表明该化合物在体内不是辅因子，也不能转化为活性辅因子。在患者的肝脏活检中未检测到GTP环化水解酶I活性。排除了患者肝脏中存在内源性抑制剂的情况。这是高苯丙氨酸血症一种新变体的首例病例，其中肝脏中二氢新蝶呤三磷酸及其蝶呤代谢产物的形成明显减少。由于尿酸水平正常，且尿液中未观察到次黄嘌呤、黄嘌呤和S-磺基半胱氨酸浓度增加，所以黄嘌呤氧化酶和亚硫酸盐氧化酶的活性正常。结论是，这些酶的钼辅因子在人体内可能并非来自二氢新蝶呤三磷酸。此外, 由于在患者的免疫系统中未发现明显异常，所以二氢新蝶呤三磷酸代谢产物，如新蝶呤，似乎不太可能像其他人所假设的那样积极参与免疫过程。见校样新增注释。
