Natural History of TANGO2 Deficiency Disorder: Baseline Assessment of 73 Patients

TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delays, seizures, intermittent ataxia, hypothyroidism and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.Data were collected from an ongoing natural history study of TDD patients enrolled between February 2019 - May 2022. Data were obtained through phone-based parent interviews and medical record review.Data were collected from 73 patients (56% male) from 57 unrelated families in 17 different countries. The median age of participants at time of data collection was 9.0 years (IQR 5.3-15.9 years, range fetal - 31 years). A total of 24 different TANGO2 alleles were observed. Patients demonstrated normal development in early infancy with progressive delays in developmental milestones thereafter. Symptoms including ataxia, dystonia and speech difficulties typically starting between the ages of 1-3 years. A total of 48 (66%) patients suffered metabolic crises and, of these, 29/48 (73%) developed cardiac crises. Metabolic crises were significantly decreased after initiation of B-complex or multivitamins.We provide the most comprehensive review of natural history of TDD and provide important observational data suggesting B-complex or multivitamins may prevent metabolic crises.