Early Initiation of B-Vitamin Supplementation May Reduce Symptoms and Explain Intrafamilial Variability: Insights From Two Sibling Pairs From the TANGO2 Natural History Study

Authors

Christina Y Miyake
Saad A Ehsan
Lilei Zhang
Samuel J Mackenzie
Mahshid S Azamian
Daryl A Scott
Andres Hernandez-Garcia
Seema R Lalani

Publication Date

9-1-2023

Journal

American Journal of Medical Genetics Part A

DOI

10.1002/ajmg.a.63331

PMID

37421366

PMCID

PMC10612108

PubMedCentral® Posted Date

9-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Vitamin B Complex, Siblings, Cognition, Genotype, Dietary Supplements, TANGO2, multivitamins, B-complex, treatment, arrhythmia, management, supplement

Abstract

TANGO2-deficiency disorder (TDD) is an autosomal recessive condition arising from pathogenic biallelic variants in the TANGO2 gene. TDD is characterized by symptoms typically beginning in late infancy including delayed developmental milestones, cognitive impairment, dysarthria, expressive language deficits, and gait abnormalities. There is wide phenotypic variability where some are severely affected while others have mild symptoms. This variability has been documented even among sibling pairs who share the same genotype, but reasons for this variability have not been well understood. Emerging data suggest a potential link between B-complex or multivitamin supplementation and decreased metabolic crises in TDD. In this report, we describe two sibling pairs from unreladiagnosed with TDD with marked differences in symptoms. In both families, the older siblings suffered multiple metabolic crises and are clinically more affected than their younger siblings who have very mild to no symptoms; they are the least impaired among 70 other patients in our ongoing international natural history study. Unlike their older siblings, the two younger siblings started taking B-complex vitamins early between 9 and 16 months. This report delineates the mildest presentation of TDD in two families. These data may support a role for early diagnosis and initiation of vitamin supplementation to not only prevent metabolic crises but also improve neurologic outcomes in this life-threatening disorder.