Huang Yue, Chang Richard, Abdenur Jose E
Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, USA.
Division of Medical Genetics, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Mol Genet Metab Rep. 2022 Jun 23;32:100885. doi: 10.1016/j.ymgmr.2022.100885. eCollection 2022 Sep.
S-Adenosylhomocysteine (SAH) hydrolase deficiency is an autosomal recessive disorder in methionine metabolism caused by pathogenic variants in the gene . To date, only 15 patients with this disorder have been reported, including several patients treated with dietary management. In this study, we report a new case with SAH hydrolase deficiency and conduct a literature review with a focus on the biochemical profiles and the efficacy of dietary management. The biochemical markers associated with SAH hydrolase deficiency includes elevated levels of methionine, creatine kinase (CK), SAH, and S-Adenosylmethionine (SAM). However, half of the cases (6/12) had normal methionine levels at the initial evaluation. In contrary, SAM and SAH were markedly elevated in all reported patients at the initial evaluation (SAM: range 1.7× -53×, median 21.5×; SAH: range 4.9× -193.8×, median 98.1×). Nine patients were treated with methionine-restricted diet, which markedly reduced SAM and SAH in all patients but the levels did not normalize. CK and liver function did not show significant improvement with dietary treatment. The majority of patients (5/8) demonstrated clinical improvements with dietary management, such as increase in muscle strength; but all patients continued to experience developmental delay and two deaths were reported from cardiopulmonary arrest. This study suggests that methionine is not a reliable diagnostic biochemical marker for SAH hydrolase deficiency and SAM/SAH levels should be considered in the workup in neonates with unexplained hypotonia, liver dysfunction, or elevated CK. Dietary restriction of methionine demonstrates clinical benefits in some affected patients and should be trialed in patients with SAH hydrolase deficiency.
S-腺苷同型半胱氨酸（SAH）水解酶缺乏症是一种由甲硫氨酸代谢中的常染色体隐性疾病，由该基因中的致病变异引起。迄今为止，仅报告了15例患有这种疾病的患者，其中包括几名接受饮食管理治疗的患者。在本研究中，我们报告了一例新的SAH水解酶缺乏症病例，并进行了文献综述，重点关注生化特征和饮食管理的疗效。与SAH水解酶缺乏症相关的生化标志物包括甲硫氨酸、肌酸激酶（CK）、SAH和S-腺苷甲硫氨酸（SAM）水平升高。然而，一半的病例（6/12）在初始评估时甲硫氨酸水平正常。相反，在所有报告的患者中，初始评估时SAM和SAH均显著升高（SAM：范围1.7× - 53×，中位数21.5×；SAH：范围4.9× - 193.8×，中位数98.1×）。9名患者接受了甲硫氨酸限制饮食，这使所有患者的SAM和SAH均显著降低，但水平未恢复正常。饮食治疗后CK和肝功能未显示出显著改善。大多数患者（5/8）通过饮食管理表现出临床改善，如肌肉力量增加；但所有患者仍有发育迟缓，并有2例因心肺骤停死亡的报告。本研究表明，甲硫氨酸不是SAH水解酶缺乏症可靠的诊断生化标志物，对于不明原因的肌张力减退、肝功能障碍或CK升高的新生儿，在检查中应考虑SAM/SAH水平。甲硫氨酸饮食限制在一些受影响的患者中显示出临床益处，对于SAH水解酶缺乏症患者应进行试验。
