Analysis of 70 patients with hydrocephalus due to cobalamin C deficiency

Abstract

Objective:To analyze the clinical characteristics of patients with hydrocephalus secondary to cblC deficiency, and to discuss the optimal strategies for assessing and treating such patients, the clinical and laboratory studies were performed in 70 patients.Methods:A total of 1211 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, 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 or /and 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, etiological treatment and prompt surgical intervention are crucial to improve the prognosis of patients.

Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review

“…In summary, ( Nogueira et al, 2008 ; Wang et al, 2010 ; Fischer et al, 2014 ; Liu et al, 2018 ; Wang et al, 2019 ; He et al, 2020a ; He et al, 2020b ; Kang et al, 2020 ; Wang et al, 2021 ), anemia is the most common blood system damage of MMA( Table 1 ), the incidence of which is 21.4–83.3%. Other hematological complications include granulocytopenia, thrombocytopenia, pancytopenia and hemolytic uremia.…”

Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis

“…Hydrocephalus is a well‐known life‐threatening complication of combined methylmalonic acidemia and homocystinuria cobalamin C type (Andersson et al, 1999 ; Zhang et al, 2019 ). Although it has been known as a rare complication of methylmalonic acidemia, a recent study reported that the complication is more common in Chinese patients with combined methylmalonic acidemia and homocystinuria cobalamin C type (He et al, 2020 ). Although the genetic diagnosis was not performed for the second baby, it is highly likely that the second baby was also affected by combined methylmalonic acidemia and homocystinuria cobalamin C type.…”

Comparing amniotic fluid mass spectrometry assays and amniocyte gene analyses for the prenatal diagnosis of methylmalonic aciduria

“…48 of them had combined MMA and homocysteinemia and 17 had isolated MMA. 222 probands got definite genetic diagnosis [ 4 , 15 ]. Mutation analysis followed the recommendations of the Human Genome Variation Society ( http://www.hgvs.org/mutnomen ).…”

“…MMA comprise a group of genetically heterogeneous autosomal recessive disorders caused by defective metabolic pathways involving methylmalonyl-CoA mutase (MUT) or its cofactor, cobalamin [ 1 , 2 ]. MMA encompass 15 diseases caused by the deficient MUT activity or other defects in adenosylcobalamin biosynthesis [ 3 , 4 ]. The clinical manifestations of the patients are complex, ranging from asymptomatic to death.…”

“…The disease could occur at any age, from prenatal to adult [ 5 , 6 ]. MMA can be diagnosed using mass spectrometry and genetic approaches [ 4 , 7 ]. With advancements in neonatal screening and selective screening, an ever-increasing number of Chinese patients are being diagnosed with clinical and genetic heterogeneous disorders.…”