Abe Yu, Aihara Yu, Endo Wakaba, Hasegawa Hiroshi, Ichida Kimiyoshi, Uematsu Mitsugu, Kure Shigeo
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Mol Genet Metab Rep. 2021 Feb 1;26:100716. doi: 10.1016/j.ymgmr.2021.100716. eCollection 2021 Mar.
Molybdenum cofactor deficiency (MoCD) is an autosomal recessive inborn error of metabolism that results from mutations in genes involved in molybdenum cofactor (Moco) biosynthesis. MoCD is characterized clinically by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. We report on a patient with an unusual late disease onset and mild phenotype, characterized by delayed development and a decline triggered by a febrile illness and a subsequent dystonic movement disorder. Magnetic resonance imaging showed abnormal signal intensities of the bilateral basal ganglia. Blood and urine chemistry tests demonstrated remarkably low serum and urinary uric acid levels. A urine sulfite test was positive. Specific diagnostic workup showed elevated levels of xanthine and hypoxanthine in serum with increased urinary sulfocysteine (SSC) levels. Genetic analysis revealed a homozygous missense mutation at c.1510C > T (p.504R > W) in exon 10 of the in isoform 7 (rs1387934803). At age 1 year 4 months, the patient was placed on a low protein diet to reduce cysteine load and accumulation of sulfite and SCC in tissues. At 3 months after introduction of protein restriction, the urine sulfite test became negative and the urine SCC level was decreased. After starting the protein restriction diet, dystonic movement improved, and the patient's course progressed without regression and seizures. Electroencephalogram findings were remarkably improved. This finding demonstrates that the dietary protein restriction suppresses disease progression in mild cases of MoCD and suggests the effectiveness of dietary therapy in MoCD.
钼辅因子缺乏症（MoCD）是一种常染色体隐性遗传的先天性代谢紊乱疾病，由参与钼辅因子（Moco）生物合成的基因突变引起。MoCD的临床特征为顽固性癫痫发作和严重、快速进展的神经退行性变，在大多数已知病例中会导致幼儿期死亡。我们报告了一名具有不寻常的疾病晚期发病和轻度表型的患者，其特征为发育迟缓以及由发热性疾病引发的病情恶化和随后出现的张力障碍性运动障碍。磁共振成像显示双侧基底神经节信号强度异常。血液和尿液化学检测显示血清和尿液尿酸水平显著降低。尿液亚硫酸盐检测呈阳性。特异性诊断检查显示血清中黄嘌呤和次黄嘌呤水平升高，尿中硫代半胱氨酸（SSC）水平增加。基因分析显示，在异构体7（rs1387934803）的第10外显子中存在c.1510C>T（p.504R>W）的纯合错义突变。在1岁4个月时，该患者开始接受低蛋白饮食，以减少组织中半胱氨酸负荷以及亚硫酸盐和SSC的积累。在引入蛋白质限制3个月后，尿液亚硫酸盐检测变为阴性，尿液SSC水平降低。开始蛋白质限制饮食后，张力障碍性运动得到改善，患者病情持续进展，未出现病情反复和癫痫发作。脑电图检查结果显著改善。这一发现表明，饮食蛋白质限制可抑制MoCD轻症病例的疾病进展，并提示饮食疗法对MoCD有效。
