TANGO2-Related Metabolic Encephalopathy and Arrhythmias

Title

Other Names:

Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration; TANGO2; Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome; Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration; TANGO2; Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome; TANGO2 related disease See More

Categories:

Congenital and Genetic Diseases; Heart Diseases; Nervous System Diseases

Summary Summary

TANGO2-related metabolic encephalopathy and arrhythmias is a disease that can cause episodes of metabolic crises and abnormal heart rhythms (arrhythmia). A metabolic crisis is caused by having low blood sugar (hypoglycemia) and the buildup of toxic products in the blood. A metabolic crisis can occur in any person with a metabolic disorder, and they are more likely to occur after a person has gone long periods without eating or during an illness. Most people with TANGO2-related metabolic encephalopathy and arrhythmias present with symptoms of a breakdown of muscle tissue (rhabdomyolysis). This can cause kidney damage and symptoms include fatigue, muscle weakness, and having a dark color of the urine. Other symptoms of TANGO2-related metabolic encephalopathy and arrhythmias include developmental delay, intellectual disability, seizures, hearing loss, low thyroid function (hypothyroidism) and trouble coordinating movements (ataxia).^[1] Signs and symptoms of the disease are most likely to first occur during infancy or early childhood.^[2] The disease is most common in people who are of Caucasian or Hispanic/Latino descent.^[3]

TANGO2-related metabolic encephalopathy and arrhythmias is caused by a genetic change (mutation or pathogenic variant) in the TANGO2 gene. The disease is inherited in an autosomal recessive manner. The disease may be suspected in people who have a metabolic crisis, episodes of rhabdomyolysis, and arrhythmias. The diagnosis can be confirmed with genetic testing. Treatment of the disease is focused on avoiding metabolic crisis by avoiding fasting or illness. If a metabolic crisis does occur, it is important to have a plan in place so that proper treatment can occur. Other symptoms of the disease may be managed with therapies and medications.^[1]

Last updated: 3/19/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
EMG: myopathic abnormalities		0003458
Increased serum lactate		0002151
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Ketonuria		0002919
30%-79% of people have these symptoms
Abnormality of extrapyramidal motor function		0002071
Acute rhabdomyolysis		0008942
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Ataxia		0001251
Compensated hypothyroidism		0008223
Delayed ability to walk		0031936
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Developmental regression	Loss of developmental milestones Mental deterioration in childhood [ more ]	0002376
Elevated hepatic transaminase	High liver enzymes	0002910
Feeding difficulties in infancy		0008872
Gastrointestinal dysmotility		0002579
Global brain atrophy	Generalized brain degeneration	0002283
Hyperammonemia	High blood ammonia levels	0001987
Incoordination	Difficulties in coordination Incoordination of limb movements Limb incoordination [ more ]	0002311
Lactic acidosis	Increased lactate in body	0003128
Moderate global developmental delay		0011343
Prolonged QT interval		0001657
5%-29% of people have these symptoms
Amblyopia	Lazy eye Wandering eye [ more ]	0000646
Babinski sign		0003487
Bilateral tonic-clonic seizure	Grand mal seizures	0002069
Cerebral visual impairment		0100704
Clonus		0002169
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Dystonia		0001332
Elevated plasma acylcarnitine levels		0045045
Focal impaired awareness seizure		0002384
Generalized myoclonic seizure		0002123
Generalized tonic seizure		0010818
Hypertonia		0001276
Hypertrophic cardiomyopathy	Enlarged and thickened heart muscle	0001639
Hypoglycemic seizures		0002173
Infantile spasms		0012469
Microcephaly	Reduced head circumference Small head circumference Decreased size of skull Decreased circumference of cranium Abnormally small skull [ more ]	0000252
Mild global developmental delay		0011342
Multifocal seizures		0031165
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Optic atrophy		0000648
Premature pubarche	Premature pubic hair growth	0012411
Premature thelarche	Premature breast development	0010314
Sensorineural hearing impairment		0000407
Severe global developmental delay		0011344
Spastic diplegia		0001264
Spastic tetraplegia		0002510
Stroke		0001297
Supranuclear gaze palsy		0000605
1%-4% of people have these symptoms
Global developmental delay		0001263
Hypoglycemia	Low blood sugar	0001943
Prolonged QTc interval		0005184
Seizure		0001250
Torsade de pointes		0001664
Ventricular tachycardia		0004756
Percent of people who have these symptoms is not available through HPO
Absent speech	Absent speech development Lack of language development Lack of speech No speech development No speech or language development Nonverbal [ more ]	0001344
Autosomal recessive inheritance		0000007
Cardiac arrest	Heart stops beating	0001695
Cerebral atrophy	Degeneration of cerebrum	0002059
Drooling	Dribbling	0002307
Dysarthria	Difficulty articulating speech	0001260
Gait ataxia	Inability to coordinate movements when walking	0002066
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hyperactive deep tendon reflexes		0006801
Hypothyroidism	Underactive thyroid	0000821
Metabolic acidosis		0001942
Muscle weakness	Muscular weakness	0001324
Myoglobinuria		0002913
Myopathic facies		0002058
Neurodegeneration	Ongoing loss of nerve cells	0002180
Oral-pharyngeal dysphagia		0200136
Poor coordination		0002370
Ventricular fibrillation		0001663

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Last updated: 7/1/2020

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Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
TANGO2 Research Foundation
300 Plaza Middlesex
Middletown, CT 06457
E-mail: info@tango2research.org
Website: http://tango2research.org/

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Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

Selected Full-Text Journal Articles

Lalani SR, Liu P, Rosenfeld JA, Watkin LB, Chiang T, Leduc MS, et al. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. Am J Hum Genet. 2018 Feb 4; 98(2):347-357.
Kremer LS, Distelmaier F, Alhaddad B, Hempel M, Iuso A, Kupper C, et al. 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.

News & Events News & Events

News

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

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References References

Lalani SR, Graham B, Burrage L, Lai YC, Scaglia F, Miyake C, and Yang Y. TANGO2-Related Metabolic Encephalopathy and Arrhythmias. GeneReviews. January 25, 2018; https://www.ncbi.nlm.nih.gov/books/NBK476443/.
Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=480864. Accessed 3/16/2018.
Lalani SR, Liu P, Rosenfeld JA, Watkin LB, Chiang T, Leduc MS, Zhu W, Ding Y, Pan S, Vetrini F, Miyake CY, et al. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. American Journal of Human Genetics. February 4, 2016; 98(2):347-357. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746334/.

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