Clinical and genetic studies on 76 patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria
10.3760/cma.j.cn112140-20210311-00204
- VernacularTitle:甲基丙二酸血症合并同型半胱氨酸尿症导致脑积水76例诊断和治疗分析
- Author:
Ruxuan HE
1
;
Hui DONG
;
Hongwu ZHANG
;
Yao ZHANG
;
Lulu KANG
;
Hui LI
;
Ming SHEN
;
Ruo MO
;
Jinqing SONG
;
Yupeng LIU
;
Zhehui CHEN
;
Yi LIU
;
Ying JIN
;
Mengqiu LI
;
Hong ZHENG
;
Dongxiao LI
;
Jiong QIN
;
Huifeng ZHANG
;
Min HUANG
;
Rongxiu ZHENG
;
Desheng LIANG
;
Yaping TIAN
;
Hongxin YAO
;
Yanling YANG
Author Information
1. 北京大学第一医院儿科 100034
- Keywords:
Methylmalonic acid;
Hyperhomocysteinemia;
Hydrocephalus;
ventriculoperitoneal shunt
- From:
Chinese Journal of Pediatrics
2021;59(6):459-465
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.
