S-Adenosylhomocysteine hydrolase deficiency:: A second patient, the younger brother of the index patient, and outcomes during therapy
S-Adenosylhomocysteine hydrolase deficiency:: A second patient, the younger brother of the index patient, and outcomes during therapy
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DOI：
10.1007/s10545-005-0192-9
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Mudd, SH
中科院分区：
文献类型：
--
作者：
Baric, I;Cuk, M;Mudd, SH
s -腺苷型同型半胱氨酸（AdoHcy）水解酶缺乏症在人类中只有一次被证实，发生在最近描述的一个克罗地亚男孩身上。在此，我们报告该先证者的弟弟的临床过程和生化异常。这个弟弟在编码adhcy水解酶的基因上也有同样的两个突变，从出生起就一直在监测。我们也报告了两名患者在治疗期间的结果。所获得的信息表明，该疾病始于子宫，主要以神经肌肉症状为特征（张力低下、行动迟缓、精神运动迟缓、肌腱反射缺失、髓鞘形成延迟）。实验室异常是明显增加肌酸激酶和升高转氨酶，以及特定的氨基酸畸变，查明病因。后者包括，最重要的，血浆adhcy显著升高。血浆s -腺苷蛋氨酸（AdoMet）也升高，蛋氨酸也升高（尽管高蛋氨酸血症在生命最初几周可能不存在或不显著）。这种疾病似乎至少在一定程度上是可以治疗的，如在限制蛋氨酸饮食和补充肌酸和磷脂酰胆碱期间，髓鞘形成和精神运动的发展得到改善。
S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine.