Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar;43(2):367-374.
doi: 10.1002/jimd.12171. Epub 2020 Jan 16.

Early neurodevelopmental characterization in children with cobalamin C/defect

Daniela Ricci  1   2 , Diego Martinelli  3 , Gloria Ferrantini  1 , Simona Lucibello  1 , MLuigia Gambardella  1 , Giorgia Olivieri  1   3 , Daniela Chieffo  1 , Domenica Battaglia  1 , Daria Diodato  3 , Giancarlo Iarossi  3 , Alice M Donati  4 , Carlo Dionisi-Vici  3 , Roberta Battini  5   6 , Eugenio M Mercuri  1   7
Affiliations

Early neurodevelopmental characterization in children with cobalamin C/defect

Daniela Ricci et al. J Inherit Metab Dis. 2020 Mar.

Abstract

Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy. Children up to the age of 4 years with a visual acuity ≥1/10 were evaluated using the Griffiths' Mental Development Scales. Eighteen children were enrolled (age range 12-48 months). Four were diagnosed by newborn screening (NBS); in the others mean age at diagnosis was 3.5 months (range 0.3-18 months). Eight had seizures: three in the first year, and five after the second year of life. Fourteen had brain lesions on magnetic resonance imaging (MRI). Neurovisual assessment evidenced low visual acuity (<3/10) in 4/18. NBS diagnosed patients had higher general and subquotients neurodevelopmental scores, normal brain MRI, and no epilepsy. The others showed a progressive reduction of the developmental quotient with age and language impairment, which was evident after 24 months of age. Our findings showed a progressive neurodevelopmental deterioration and a specific fall in language development after 24 months in cblC defect. The presence of brain lesions and epilepsy was associated with a worst neurodevelopmental outcome. NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have a protective effect on the development of brain lesions and to promote a more favorable neurodevelopment.

Keywords: children; cobalamin C; language; neonatal screening; neurodevelopment; visual acuity.

PubMed Disclaimer

References

REFERENCES

    1. Carrillo-Carrasco N, Venditti CP. Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes. J Inherit Metab Dis. 2012;35:103-114.
    1. Rosenblatt DS, Aspler AL, Shevell MI, Pletcher BA, Fenton WA, Seashore MR. Clinical heterogeneity and prognosis incombined methylmalonic aciduria and homocystinuria (Cbl-C). J Inherit Metab Dis. 1997;20:528-538.
    1. Fischer S, Huemer M, Baumgartner M, et al. Clinical presentation and outcome in a series of 88 patients with the cblC defect. J Inherit Metab Dis. 2014;37:831-840.
    1. Huemer M, Diodato D, Martinelli D, et al. Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: data from the E-HOD registry. J Inherit Metab Dis. 2019;42:333-352.
    1. Longo D, Fariello G, Dionisi-Vici C, et al. MRI and 1H-MRS findings in early-onset cobalamin C/D defect. Neuropediatrics. 2005;36:366-372.