Infantile tremor syndrome and laryngomalacia: A novel association?

Abstract

Infantile tremor syndrome (ITS) is a rare clinical entity, predominantly characterized by coarse tremors, regression of motor and/or cognitive, and language milestones. Although the exact pathogenesis yet remains to be unknown, various micronutrient deficiencies like vitamin B12, zinc, magnesium, and vitamin C have been shown to be associated with ITS. Vitamin B12 deficiency is the most accepted etiology of this entity. Here we are describing a seemingly novel association of laryngomalacia with infantile tremor syndrome. Clinical details, laboratory investigations, demographic and socioeconomic parameters of all children<2 years of age, diagnosed with ITS between August 2019 and November 2020 was obtained by a retrospective chart review. The study population was divided into two subgroups based on the presence/absence of laryngomalacia and different variables were compared between the two subgroups. During the study period, 22 ITS and 13 pre-ITS cases were identified, out of which 5 ITS cases had laryngomalacia, the prevalence is higher as compared to estimated prevalence in reported literature (p<0.0001). All these 5 cases had associated gastro-esophageal reflux and swallowing dysfunction and all of them were managed conservatively, apart from standard care treatment for ITS. On follow-up, all 5 of them showed improvement in symptoms of laryngomalacia, apart from clinical and hematological improvement. Differences between various clinical and biochemical parameters in the subgroup with and without laryngomalacia were not significantly different. Seventeen out of twenty-two children with ITS and 10/13 children with pre-ITS had macrocytic anemia and the rest had dimorphic anemia on peripheral smear. There was moderate vitamin B12 deficiency in 13/22 and 8/13 children with ITS and pre-ITS respectively, and the rest had a severe vitamin B12 deficiency. Clinicians need to screen cases with ITS for probable symptoms of laryngomalacia and accordingly advise management measures. Although our study showed a seemingly apparent association between ITS and laryngomalacia, large prospective controlled studies with long-term follow-up are necessary to prove this association.