The biochemistry behind Infantile Tremor Syndrome

 

A 9 month old baby came in with progressive hyperpigmentation for 15 days, tremors and altered sensorium for 5 days.

His haemoglobin was 7.7gm/dl with an MCV of 96fl. His MRI brain showed a predominant fronto-temporal atrophy and some mild delay in myelination. His Serum Vitamin B12 was low and serum homocysteine was elevated.

No marks for making the diagnosis of Infantile Tremor Syndrome (ITS). He had been inadequately weaned and was predominantly on breast feeds. His mother was a strict vegetarian. All this tied in very well with the classical picture of ITS. The clouds of doubt about the underlying ethology are slowly dissipating in the face of strong evidence that the culprit is vitamin B12 deficiency.

Studies from PGI Chandigarh in 92 children have shown that though Vitamin B12 levels are documented to be low in about 42%, serum homocysteine is a better marker and is elevated in 96.5 %. An MCV > 95fl is again seen in a mere 42 %.https://doi.org/10.1007/s12098-019-03117-w

If you have inadvertently done an  acylcarnitine profile you may pick up elevated C3/C2 and C3/C16 levels. Urine organic acids will show elevated methylmalonic acid levels.

How does cobalamin deficiency result in such widespread neurological deficits in the brain?

Cobalamine in the brain is in 2 forms - adenosylcobalamine and methylcobalamin. Both have a role to play.

Adenosyl cobalamin converts methylmalonyl CoA  to succinylcholine CoA. In its absence excess of propionyl CoA is formed and subsequently odd chain fatty acids. These C15, C17 fatty acids when incorporated into the myelin are defective. Hence the abnormal myelination and developmental delay.

Methycobalamin deficiency on the other hand impairs conversion of homocysteine to methionine which in turn is the precursor of an important methyl donor for various fatty acids in myelin.