From the Departments of Pediatrics (R.H., L.K., Y.Z., R.M., J.S., Z.C., Yi Liu, Y.J., M.L., H.D., Y.Y.) and Pediatric Surgery (H.Z., H.L., H.Y.), Peking University First Hospital; Translational Medicine Center (M.S., Y.T.), Chinese PLA General Hospital; Department of Pediatrics (Yupeng Liu, J.Q.), People's Hospital of Peking University, Beijing; Department of Pediatrics (H.Z.), First Affiliated Hospital of Henan University of Traditional Chinese Medicine; Department of Endocrinology and Genetic (D. Li), Henan Children's Hospital, Zhengzhou; Department of Pediatrics (H.Z.), Hebei Medical University Second Hospital, Shijiazhuang; Similan Clinic, (M.H.) Beijing; and School of Life Sciences (D. Liang), Central South University, Changsha, China.
Neurology. 2020 Dec 8;95(23):e3129-e3137. doi: 10.1212/WNL.0000000000010912. Epub 2020 Sep 17.
To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients.
A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis.
Of the 70 patients, 67 (95.7%) had early-onset MMA and homocystinuria. The patients typically had high blood propionylcarnitine and total homocysteine, low methionine, and methylmalonic aciduria. Signs of intracranial hypertension were relatively rare. We measured ventricular dilatation early in the disease by cranial ultrasound and MRI and/or CT. Eighteen different mutations, including 4 novel mutations (c.427C>T, c.568insT, c.599G>A, and c.615C>A), were identified biallelically in all 70 patients. c.609G>A was the most frequent mutation, followed by c.658_660del, c.217C>T, and c.567dupT. Three cases were diagnosed by postmortem study. Metabolic therapy, including cobalamin injections supplemented with oral l-carnitine and betaine, was administered in the remaining 67 cases. A ventriculoperitoneal shunt was performed in 36 cases. During the follow-up, psychomotor development, nystagmus, impaired vision, and sunset eyes improved gradually.
Hydrocephalus is a severe condition with several different causes. In this study, ventriculomegaly was found in 70 patients with cblC deficiency. Early diagnosis, etiologic treatment, and prompt surgical intervention are crucial to improve the prognosis of patients.
通过对 70 例患者的临床和实验室研究，分析钴胺素 C(cblC)缺乏继发脑积水患者的临床特征，并探讨评估和治疗此类患者的最佳策略。
1998 年至 2019 年，共有 1211 例患者临床诊断为甲基丙二酸血症(MMA)。其中，70 例脑积水患者经脑影像学和生化及基因分析证实为 cblC 缺乏。
70 例患者中，67 例(95.7%)有早发型 MMA 和高同型半胱氨酸血症。患者通常血丙酰肉碱和总同型半胱氨酸升高，蛋氨酸和甲基丙二酸尿降低。颅内高压征象相对少见。我们通过头颅超声、MRI 和/或 CT 早期测量疾病脑室扩张。在所有 70 例患者中，均发现 18 种不同的突变，包括 4 种新突变(c.427C>T、c.568insT、c.599G>A 和 c.615C>A)，均为双等位基因突变。c.609G>A 是最常见的突变，其次是 c.658_660del、c.217C>T 和 c.567dupT。3 例为尸检诊断。在 67 例存活患者中给予代谢治疗，包括钴胺素注射，辅以口服左卡尼汀和甜菜碱。36 例行脑室-腹腔分流术。在随访中，精神运动发育、眼球震颤、视力障碍和落日眼逐渐改善。
脑积水是一种严重的疾病，病因多样。在本研究中，我们发现 cblC 缺乏症患者存在脑室扩大。早期诊断、病因治疗和及时手术干预对改善患者预后至关重要。
