TANGO2 deficiency in siblings

*Correspondence: [e-mail].

Abstract

Case Presentation: Case 1: A male child had normal neurological development until one year old. Then, he started having episodes of vomit and diarrhea, followed by hypoglycemia and seizures. These events were followed by regression in his development, cognitive decline and progressive spastic tetraparesis. During the investigation, he was also diagnosed with hypothyroidism and epilepsy. Brain magnetic resonance imaging (MRI) had diffused cerebral and cerebellar atrophy, along with a thin corpus callosum. Whole exome sequencing (WES) showed a pathogenic variant in TANGO2, which allowed the diagnosis of TANGO2 deficiency. Case 2: During the investigation of patient of case one, the younger sister presented a similar story. Normal development until 15 months old, when the first metabolic crisis occurred. Patient needed support of the pediatric intensive care unit (PICU) and intubation. Afterwards, she developed epilepsy, hypotonia, gait impairment and development regression. Further genetic investigation showed the same pathogenic variant in TANGO2 as in her brother.

Discussion: Pathogenic variants in TANGO2 (Transport and Golgi Organizations 2 Homolog) were first identified in 2016. Patients present with global developmental delay, ataxia, epilepsy, progressive cognitive decline, encephalopathy, hypothyroidism and life-threatening metabolic crisis with hypoglycemia, rhabdomyolysis, cardiac arrhythmias and cardiomyopathy. Symptoms usually start in infancy and developmental delay is often the first sign. It is an autosomal recessive condition and the diagnosis of patients with suggestive phenotype occurs by the identification of biallelic pathogenic variants in TANGO2. Also, in metabolic crisis, elevated creatine phosphokinase (CPK) and liver enzymes, along with hypoglycemia, lactic acidosis, mild hyperammonemia and QTc prolongation can be found. Imaging shows diffuse atrophy, ventriculomegaly and diminished white matter. There is no specific treatment. Daily supplementation of B Complex vitamins is indicated, along with antiepileptic drug therapy (AED), levothyroxine as needed, rehabilitation therapies and psychological support for patients and caregivers. During the acute metabolic crisis, support care is needed to acknowledge the complications, such as hypoglycemia, arrhythmias and rhabdomyolysis.

Final Comments: TANGO2 deficiency is a rare condition with poor prognosis. However, knowing this disorder is important in order to prevent recurrent crises and improve patients’ and caregivers’ quality of life.

 

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Publication History

Article published online:
12 May 2025