Clinical presentation and outcome in a series of 88 patients with the cblC defect

Abstract

No major differences were found between neonatal and early onset patients so that these groups were combined as an infantile-onset group representing 88 % of all cases. Hypotonia, lethargy, feeding problems and developmental delay were predominant in this group, while late-onset patients frequently presented with psychiatric/behaviour problems and myelopathy. Plasma total homocysteine was higher and methionine lower in infantile-onset patients. Plasma methionine levels correlated with "overall impression" as judged by treating physicians. Physician's impression of patient's well-being correlated with assessed disease load. We confirmed the association between homozygosity for the c.271dupA mutation and infantile-onset but not between homozygosity for c.394C>T and late-onset. Patients were treated with parenteral hydroxocobalamin, betaine, folate/folinic acid and carnitine resulting in improvement of biochemical abnormalities, non-neurological signs and mortality. However the long-term neurological and ophthalmological outcome is not significantly influenced. In summary the survey points to the need for prospective studies in a large cohort using agreed treatment modalities and monitoring criteria.

Do not Miss Rare and Treatable Cause of Early-Onset Hemolytic Uremic Syndrome: Cobalamin C Deficiency

“…Fischer et al [22] showed that treatment with parenteral hydroxocobalamin, betaine, folate/folinic acid, and carnitine improved biochemical abnormalities, but long-term neurological and ophthalmological outcomes were not affected significantly. On the contrary, in patient 1, neurological signs improved after proposed treatment.…”

A Highly Diverse Portrait: Heterogeneity of Neuropsychological Profiles in cblC Defect

“…Dietary methionine provides a source of methionine that may compensate in part for the defective intracellular synthesis of methionine that follows closely from the primary defect in cblC. Although patients with cblC were traditionally restricted in protein intake, in a recent survey, none of 88 European patients received protein restriction (Fischer et al 2014). Furthermore, recent studies of treatment in cblC found no benefit in restricting protein access and a possibly deleterious effect of using low-methionine medical foods (Manoli et al 2015).…”

“…Characteristic clinical manifestations of the early-onset type include feeding difficulties, failure to thrive, developmental delay, and muscular hypotonia (e.g., Fischer et al 2014;Rosenblatt et al 1997). Some earlyonset patients develop a hemolytic-uremic-like syndrome, optic atrophy, and congenital or acquired cardiomyopathy (Martinelli et al 2011), sometimes with noncompaction (Profitlich et al 2009).…”

“…Some earlyonset patients develop a hemolytic-uremic-like syndrome, optic atrophy, and congenital or acquired cardiomyopathy (Martinelli et al 2011), sometimes with noncompaction (Profitlich et al 2009). Other clinical signs include proteinlosing enteropathy, pulmonary hypertension (Iodice et al 2013), acidosis, and hyperammonemia (Fischer et al 2014;Martinelli et al 2011). Although cblC is part of a group of conditions that are accompanied by an elevation of both homocystine and methylmalonic acid in blood and plasma, it is clinically unique because some features are reported only in this defect, such as the distinct maculopathy (Gizicki et al 2014;Weisfeld-Adams et al 2015) and hemolytic-uremic-like syndrome.…”

Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level

“…Early-onset patients present with intrauterine growth retardation (IUGR), microcephaly, failure to thrive, developmental delay, hypotonia, progressive retinopathy, and maculopathy (Fischer et al 2014). Early-onset patients usually present in the first months of life and have an unfavorable prognosis (CarrilloCarrasco et al 2011).…”