Unveiling Nutritional Disparities in Infantile Tremor Syndrome: A Focus on Holo-Transcobalamin and Essential Fatty...

Infantile tremor syndrome (ITS), a self-limiting disorder prevalent in the Indian subcontinent, is characterized by tremors, anemia, pigmentary skin changes, developmental delay or regression, and hypotonia. Although a nutritional etiology is suspected, particularly vitamin B12 deficiency, the roles of the bioactive marker holo-transcobalamin (holo-TC) and essential fatty acids (EFAs) remain unexplored. This comparative pilot study was conducted from December 1, 2023, to April 30, 2024, at Government Medical College, Datia, India. The study included 14 infants who were assigned to two groups. Group 1 (n = 7) comprised infants with ITS and tremors, and Group 2 (n = 7) included those with ITS without tremors to assess threshold-dependent biochemical markers across this clinical spectrum. Laboratory investigations included complete hemogram, serum vitamin B12, holo-TC, and EFA profiles. Data were summarized using medians and interquartile ranges. Between-group differences were expressed as effect sizes (median differences) with 95% confidence intervals. Severe developmental delays were more frequent in Group 1 (5/7) than in Group 2 (mild to moderate in 4/7). Both groups were anemic and had low serum vitamin B12 levels (median: 188 pg/mL in Group 1 vs. 198 pg/mL in Group 2). Holo-TC was undetectable (< 5 pmol/L) in Group 1 and in only one patient from Group 2 (median: 10.12 pmol/L in the remaining Group 2 patients). Macrocytosis was higher in Group 1 (median MCV: 98 fL vs. 75.5 fL), with a median difference of 22.5 fL (95% CI: 6.8 to 38.2). Clinical examination also revealed characteristic hair hypochromotrichia and progressive regression in both phenotypes. Both groups exhibited low omega (ω)-3 fatty acid levels, elevated saturated fatty acid levels, and high ω-6:ω-3 ratios (median: approximately 10:1), with small and imprecise between-group differences (confidence intervals crossing zero). Extremely low holo-TC levels were strongly associated with tremors in ITS, suggesting that holo-TC is a superior marker of bioactive vitamin B12 deficiency and a critical metabolic threshold for tremor manifestation. EFA imbalances were prevalent in both groups but not specific to tremor incidence, highlighting the need for larger studies. The overall pathophysiology points toward significant maternal nutritional depletion during pregnancy and lactation as the relevant origin of the syndrome.