Natural History Study and Establishment of a Biorepository-TANGO2-related Disorder

The study aims to establish a biorepository of individuals with TANGO2 deficiency to support scientific research and establish a comprehensive clinical database of affected individuals to understand the disease course.

Study Overview

• Status: Recruiting
• Conditions: TANGO2-related Disorder
• Intervention / Treatment: Genetic: Observation

Detailed Description

TANGO2-related disorder is a rare autosomal recessive genetic disorder that can cause recurrent rhabdomyolysis and life-threatening cardiac arrhythmias. Metabolic crises can be triggered by prolonged fasting and dehydration. Intellectual disability, seizures, hypothyroidism, and gait abnormalities are observed frequently. The function of TANGO2 is unknown and the pathogenesis of this disease is poorly understood. Understanding disease mechanism requires studying disease cells/samples and thus establishing a biobank of tissues (blood and fibroblasts) of individuals affected with TANGO2 deficiency is paramount. Natural History Study of TANGO2-related disorder will allow investigators to understand the course of the disease and develop new therapies in the future to decrease morbidity associated with this genetic condition.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Christina Miyake, MD; Phone Number: 832-824-3278; Email: cymiyake@bcm.edu
      • Contact: Seema Lalani, MD; Phone Number: 832-822-4280; Email: seemal@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Individuals with TANGO2-related disorder with any of the following conditions will be recruited: Recurrent rhabdomyolysis, cardiac arrhythmias, muscle weakness, ataxia, progressively unsteady gait, intellectual disability, hypothyroidism, and seizures.

Description

Inclusion Criteria:

All patients with pathogenic TANGO2 variants will be included.

Exclusion Criteria:

Patients who do not have TANGO2-related disease will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with TANGO2 deficiency; Individuals with TANGO2 deficiency known to have disease causing variants in TANGO2	Genetic: Observation; Retrospective and prospective Natural History Study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with metabolic and cardiac crisis assessed by the number of hospitalizations	Detailed interview with participants and review of medical records will be used to assess the frequency and triggers of metabolic and cardiac crises	10 years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Tango2 Research Foundation

Publications and helpful links

General Publications

• Lalani SR, Liu P, Rosenfeld JA, Watkin LB, Chiang T, Leduc MS, Zhu W, Ding Y, Pan S, Vetrini F, Miyake CY, Shinawi M, Gambin T, Eldomery MK, Akdemir ZH, Emrick L, Wilnai Y, Schelley S, Koenig MK, Memon N, Farach LS, Coe BP, Azamian M, Hernandez P, Zapata G, Jhangiani SN, Muzny DM, Lotze T, Clark G, Wilfong A, Northrup H, Adesina A, Bacino CA, Scaglia F, Bonnen PE, Crosson J, Duis J, Maegawa GH, Coman D, Inwood A, McGill J, Boerwinkle E, Graham B, Beaudet A, Eng CM, Hanchard NA, Xia F, Orange JS, Gibbs RA, Lupski JR, Yang Y. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. Am J Hum Genet. 2016 Feb 4;98(2):347-57. doi: 10.1016/j.ajhg.2015.12.008. Epub 2016 Jan 21.
• Kremer LS, Distelmaier F, Alhaddad B, Hempel M, Iuso A, Kupper C, Muhlhausen C, Kovacs-Nagy R, Satanovskij R, Graf E, Berutti R, Eckstein G, Durbin R, Sauer S, Hoffmann GF, Strom TM, Santer R, Meitinger T, Klopstock T, Prokisch H, Haack TB. Bi-allelic Truncating Mutations in TANGO2 Cause Infancy-Onset Recurrent Metabolic Crises with Encephalocardiomyopathy. Am J Hum Genet. 2016 Feb 4;98(2):358-62. doi: 10.1016/j.ajhg.2015.12.009. Epub 2016 Jan 21.
• Milev MP, Saint-Dic D, Zardoui K, Klopstock T, Law C, Distelmaier F, Sacher M. The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER-to-Golgi transport and at the mitochondria. J Inherit Metab Dis. 2021 Mar;44(2):426-437. doi: 10.1002/jimd.12312. Epub 2020 Sep 21.
• Berat CM, Montealegre S, Wiedemann A, Nuzum MLC, Blondel A, Debruge H, Cano A, Chabrol B, Hoebeke C, Polak M, Stoupa A, Feillet F, Torre S, Boddaert N, Bruel H, Barth M, Damaj L, Abi-Warde MT, Afenjar A, Benoist JF, Madrange M, Caccavelli L, Renard P, Hubas A, Nusbaum P, Pontoizeau C, Gobin S, van Endert P, Ottolenghi C, Maltret A, de Lonlay P. Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect. J Inherit Metab Dis. 2021 Mar;44(2):415-425. doi: 10.1002/jimd.12314. Epub 2020 Sep 28.
• Powell AR, Ames EG, Knierbein EN, Hannibal MC, Mackenzie SJ. Symptom Prevalence and Genotype-Phenotype Correlations in Patients With TANGO2-Related Metabolic Encephalopathy and Arrhythmias (TRMEA). Pediatr Neurol. 2021 Jun;119:34-39. doi: 10.1016/j.pediatrneurol.2021.02.011. Epub 2021 Mar 8.
• Heiman P, Mohsen AW, Karunanidhi A, St Croix C, Watkins S, Koppes E, Haas R, Vockley J, Ghaloul-Gonzalez L. Mitochondrial dysfunction associated with TANGO2 deficiency. Sci Rep. 2022 Feb 23;12(1):3045. doi: 10.1038/s41598-022-07076-9.
• Miyake CY, Burrage L, Glinton K, Houck K, Hoyos-Martinez A, Graham B, Yang Y, Rawls-Castillo B, Scaglia F, Soler-Alfonso C, Lalani SR. TANGO2 Deficiency. 2018 Jan 25 [updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK476443/

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2018
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: H-43240

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No