This report describes TANGO2-related metabolic encephalopathy and arrhythmias, which exhibits autosomal recessive inheritance. The human gene implicated is TANGO2, which encodes transport and golgi organization 2 homolog, There is one high-scoring fly ortholog, Dmel\Tango2, for which a loss-of-function allele, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
Human TANGO2 has not been introduced into flies.
Flies bearing a loss-of-function allele of Dmel\Tango2 exhibit multiple behavioral phenotypes consistant with with those of the human disease, including metabolic crisis in response to starvation, heat-induced seizures, learning deficits, and motor defects. The behavior phenotypes of affected flies are partially ameliorated by treatment with pantothenic acid (vitamin B5).
[updated June 2023 by FlyBase; FBrf0222196]
[METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION; MECRCN](https://omim.org/entry/616878)
[TRANSPORT AND GOLGI ORGANIZATION 2 HOMOLOG; TANGO2](https://omim.org/entry/616830)
TANGO2 deficiency is characterized by developmental delay, intellectual disability, gait incoordination, speech difficulties, seizures, and hypothyroidism. Most individuals have TANGO2 spells, non-life-threatening paroxysmal worsening of baseline symptoms, including sudden onset of hypotonia, ataxia with loss of balance, head and body tilt, increased dysarthria, drooling, lethargy, and disorientation. In addition, life-threatening acute metabolic crises can occur, including rhabdomyolysis with elevated creatine phosphokinase and liver transaminases, hypoglycemia, prolonged QTc on EKG, ventricular arrhythmias, and/or cardiomyopathy. [from GeneReviews:NBK476443 2023.03.09]
TANGO2-related metabolic encephalopathy and arrhythmias is an autosomal recessive disorder characterized by episodic metabolic degeneration affecting skeletal muscle, cardiac muscle, and the nervous system. Affected individuals usually present in childhood with acute encephalomyopathic features, including rhabdomyolysis, hypotonia, and neurologic regression, although most patients have delayed psychomotor development before the acute onset. The overall disease course is characterized by progressive neurodegeneration with epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Cardiac involvement with severe arrhythmias is a consistent and potentially life-threatening manifestation (summary by Lalani et al., 2016, pubmed:26805781; and Kremer et al., 2016, pubmed:26805782). [from MIM:616878; 2023.06.27]
TANGO2-related metabolic encephalopathy and arrhythmias is caused by homozygous compound heterozygous mutation in the TANGO2 gene on chromosome 22q11. [from MIM:616878; 2023.06.27]
Proteins of the TANGO family, such as TANGO2, are predicted to function in cargo loading of newly synthesized secretory proteins in the endoplasmic reticulum (summary by Lalani et al., 2016 pubmed:26805781). [from MIM:616830; 2023.06.27]
One to one (1 human to 1 Drosophila); TANGO2 has one high-scoring Drosophila ortholog, Tango2.
High-scoring ortholog of human TANGO2 (1 Drosophila to 1 human).
