Ruxuan He1, Hongwu Zhang1, Lulu Kang1, Hui Li1, Ming Shen1, Yao Zhang1, Ruo Mo1, Yupeng Liu1, Jinqing Song1, Zhehui Chen1, Yi Liu1, Ying Jin1, Mengqiu Li1, Hui Dong1, Hong Zheng1, Dongxiao Li1, Jiong Qin1, Huifeng Zhang1, Min Huang1, Desheng Liang1, Yaping Tian1, Hongxin Yao2, Yanling Yang2. 1. 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. 2. 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. yaohongxin2012@sina.com organic.acid@vip.126.com.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 MMACHC 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. CONCLUSION: 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.
OBJECTIVE: To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalaminC (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients. METHODS: 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. RESULTS: 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 MMACHC 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. CONCLUSION: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.
Authors: Anna J Esser; Srijan Mukherjee; Ilia A Dereven'kov; Sergei V Makarov; Donald W Jacobsen; Ute Spiekerkoetter; Luciana Hannibal Journal: iScience Date: 2022-08-18