# TANGO2 deficiency disorder in a 61-year-old male with episodic weakness, rhabdomyolysis, myotonia, and a novel missense variant

## TL;DR

A 61-year-old man with TANGO2 deficiency disorder, the oldest known case, shows a novel genetic variant and milder symptoms.

## Contribution

This is the first reported case of TANGO2 deficiency in an adult over 60 and suggests a possible genotype-phenotype correlation.

## Key findings

- The patient had a deletion of exons 3–9 in TANGO2 and a novel missense variant (p.Gly63Cys).
- The patient showed improvement with vitamin B-complex and pantothenic acid supplementation.
- This case may represent the first example of genotype-phenotype correlation in TANGO2 deficiency disorder.

## Abstract

TANGO2 Deficiency Disorder (TDD) is an autosomal recessive condition, most commonly diagnosed in childhood. Clinical features may include episodic movement disorders, seizures, cognitive impairment, hypothyroidism, and metabolic crises marked by rhabdomyolysis and life-threatening cardiac symptoms. A small number of adults, thought to largely represent the milder end of the phenotypic spectrum, have received a diagnosis of TDD in their 30's or 40's, though no genotype-phenotype correlations have been established to date. In this case report, we present a 61-year-old man with mild intellectual disability and recurrent muscle weakness who was diagnosed with TDD during an inpatient hospitalization for diverticulitis, prostatitis, and muscle weakness, ultimately attributed to rhabdomyolysis. Genetic testing revealed a deletion of exons 3–9 in TANGO2 along with a novel missense variant (c.187G > T; p.Gly63Cys) on the other allele. The patient was started on vitamin B-complex with additional pantothenic acid (500 mg daily) and subsequently noted improvement in his speech and energy levels. To our knowledge, this case describes the oldest known individual living with TDD by two decades. Additionally, the patient's relatively mild symptom profile and previously unreported missense variant in TANGO2 may represent the first known example of genotype-phenotype correlation in TDD.

•TANGO2 Deficiency Disorder (TDD) is a rare autosomal recessive condition typically diagnosed in childhood•This case report describes a 61-year-old man with TDD, the oldest known person living with the condition•The p.Gly63Cys variant in TANGO2 has not been previously described and may be associated with a less severe phenotype•TDD should be part of the differential diagnosis for patients with episodic weakness, rhabdomyolysis, and myotonia

TANGO2 Deficiency Disorder (TDD) is a rare autosomal recessive condition typically diagnosed in childhood

This case report describes a 61-year-old man with TDD, the oldest known person living with the condition

The p.Gly63Cys variant in TANGO2 has not been previously described and may be associated with a less severe phenotype

TDD should be part of the differential diagnosis for patients with episodic weakness, rhabdomyolysis, and myotonia