Infantile Seizures and Regression Secondary to Maternal Vitamin B12 Deficiency: A Treatable Neurodevelopmental Disorder
Meghna Rajaprakash1, Nadav Weinstock2, Jacqueline Wood3, Emily DeBoy2, Alexander Testino2, Carl Stafstrom2, Gerald Raymond1, Hilary Vernon1
1Kennedy Krieger Institute, Johns Hopkins School of Medicine, 2Johns Hopkins School of Medicine, 3Pheonix Children's Hospital
Background:
Metabolic disease is an important and potentially treatable cause of infantile seizures and developmental epileptic encephalopathies (DEEs). While next-generation sequencing (NGS) has transformed diagnostic evaluation, reliance on molecular testing may overlook biochemical abnormalities secondary to nutritional deficiencies. Early identification of these conditions is critical, as prompt intervention can prevent irreversible neurological injury and developmental delays.
Results:
We report an 11-month-old male who presented with six months of progressive failure to thrive, developmental regression, hypotonia, aversion to solids, and infantile seizures and spasms. Systemically, he developed macrocytic anemia, neutropenia, and oral mucocutaneous lesions. Neuroimaging revealed a thin corpus callosum, and initial EEG demonstrated multifocal epileptiform discharges. Initial metabolic screening showed elevated propionylcarnitine (C3), methylmalonic acid (MMA), and total plasma homocysteine (pHCy), with low-normal serum vitamin B12. Rapid whole exome sequencing was unremarkable, raising suspicion for either an unrecognized inborn error of cobalamin metabolism or secondary B12 deficiency. Further investigation revealed that the child was exclusively breastfed by a mother with undiagnosed pernicious anemia and undetectable vitamin B12 levels. The infant was diagnosed with secondary nutritional cobalamin deficiency. Vitamin B12 supplementation led to rapid normalization of metabolic markers and clinical improvement was observed, including resolution of infantile spasms with corticosteroid therapy, normalization of EEG and brain MRI findings, and improved developmental metrics.
Conclusions:
This case highlights that nutritional vitamin B12 deficiency, though rare in developed settings, remains an important and reversible cause of developmental regression, hypotonia, and seizures in infancy especially in exclusively breastfed infants. It underscores the limitations of relying solely on genetic sequencing for DEE evaluation and emphasizes the importance of metabolic testing in all infants with unexplained regression or refractory seizures. Recognition of maternal Vitamin B12 deficiency is essential and should be screened, as early treatment can prevent long-term neurological sequelae and significantly improve developmental outcomes.
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