Early neurodevelopmental characterization in children with cobalamin C/defect.

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism.
• Commonly presents with developmental delay, behavioral issues, and maculopathy, requiring systematic investigation.
• Early neurodevelopmental outcomes and contributing factors in cblC patients are not well-defined.

Purpose of the Study:

• To define early neurodevelopment in cblC patients.
• To investigate the contribution of diagnosis mode, age at diagnosis, brain lesions, and epilepsy to neurodevelopmental outcomes.
• To assess the impact of newborn screening (NBS) on cblC defect outcomes.

Main Methods:

• Evaluation of 18 children (12-48 months) with cblC defect using Griffiths' Mental Development Scales.
• Assessment of neurovisual acuity and brain lesions via MRI.
• Comparison of outcomes between patients diagnosed via NBS and those diagnosed later.

Main Results:

• Newborn screening diagnosed patients exhibited higher neurodevelopmental scores, normal MRIs, and no epilepsy.
• Patients diagnosed later showed progressive neurodevelopmental decline, particularly in language after 24 months.
• Brain lesions and epilepsy were associated with poorer neurodevelopmental outcomes.

Conclusions:

• Cobalamin C defect leads to progressive neurodevelopmental deterioration, with a specific decline in language after 24 months.
• Early diagnosis through newborn screening offers a protective effect, preventing brain lesions and promoting better development.
• Intervention strategies should focus on early detection and treatment to improve long-term outcomes in cblC patients.