The neurological syndrome of infantile cobalamin deficiency: Developmental regression and involuntary movements

Abstract

Developmental regression is the presenting symptom of most infants with cobalamin (Vitamin B12) deficiency. We present a report of three infants with cobalamin deficiency in which the infants also developed a movement disorder. In each case the mother was a vegetarian and the infant was exclusively breast-fed. In two of the infants, a striking movement disorder consisting of a combination of tremor and myoclonus particularly involving face, tongue, and pharynx appeared 48 h after the initiation of treatment with intramuscular cobalamin. This was associated with marked changes in plasma amino acid levels. Paradoxically, the onset of the movement disorder coincided with overall neurological improvement. The third infant had a persistent focal tremor, which appeared before the commencement of treatment. The movements slowly abated during a 3-6 week period. The presence of a movement disorder in cobalamin deficiency has received less attention than other features, but in a mild form is probably common. It may offer an early clue to the diagnosis before the onset of profound neurological deterioration. The cause of the severe movement disorder that can appear after treatment is not known.

Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism

“…B12 deficiency is well known to have neuropsychiatric consequences in adults (Zucker et al 1981) and adversely affect neurodevelopment during infancy (Graham et al 1992). In toddlers, severe B12 deficiency has been associated with developmental regression similar to that observed in ~33% of autistic children (Grattan-Smith et al 1997). It is provocative to note that the TCN2 GG variant would be expected to negatively affect B12 cofactor availability for the methionine synthase reaction just as the interaction between RFC-1 80G and MTHFR 677T alleles would be expected to reduce methylfolate availability for the same methionine synthase reaction.…”

Involuntary movements during vitamin B12 treatment in infants

“…The duration of movement disorder is 10-30 d. The severity, nature, and timing of movement disorder are highly variable [1,4,7]. Jadhav et al [9] first described nutritional vitamin B12 deficiency in 6 Indian infants aged 6-12 months that presented with megaloblastic anemia, psychomotor regression, and hyper pigmentation of the skin.…”

“…Some studies have shown that congenital anomalies in homocysteine remethylation or an abnormality in the methionine synthetase reaction leads to neurological symptoms [3,15]. Grattan-Smith et al [4] suggested that movement disorder in such cases is due to hyper activation of metabolic pathways that contain vitamin B12, and temporary vitamin B12 or folate metabolism imbalance. Changes in the plasma concentration of various amino acids were observed in response to vitamin B12 treatment.…”

“…Although clinical findings show that vitamin B12 deficiency can be tolerated by adults for many years due to their endogenous reserve, in infants it may produce symptoms 2-12 months following birth due to an inadequate hepatic reserve [1][2][3][4][5][6]. Patients with vitamin B12 deficiency present with hematological, neurological, and psychiatric symptoms, which are more commonly observed in adults.…”

“…Severe neurological findings, such as hypotonia, apathy, decreased eye contact, involuntary movement, seizure, lethargy, and coma, have been reported [1,3,4,7,8]. A delay in the diagnosis and treatment of vitamin B12 deficiency can lead to irreversible psychomotor retardation and neurological damage.…”