Paroxysmal neurological spells in TANGO2 deficiency disorder: a case report and a scoping review

TANGO2 deficiency disorder (TDD) is a rare autosomal recessive condition characterized by neurodevelopmental impairment and recurrent metabolic crises. Paroxysmal non-epileptic neurological episodes ("TANGO2 spells") are increasingly recognized but remain poorly characterized and often misdiagnosed.

We report a child with TDD presenting with recurrent paroxysmal neurological episodes and performed a scoping review of Scopus and PubMed-indexed literature to summarize clinical features, triggers, diagnostic findings and management of TANGO2 spells.

The reported patient developed recurrent stereotyped episodes from 23 months of age, characterized by weakness, dystonia with head tilt, vomiting, irritability and reduced responsiveness, lasting several hours and triggered by illness or reduced intake. EEG during spells was without epileptic discharges, metabolic investigations and QTc were normal, and whole-exome sequencing confirmed biallelic pathogenic TANGO2 variants. Following supportive supplementation, no further spells or metabolic crises occurred. Across 7 studies including 93 patients identified by the scoping review, TANGO2 spells typically began in infancy or early childhood, were stress-related, transient, and self-limited, with non-ictal EEG findings when assessed. Cardiac involvement was consistently associated with metabolic crises rather than isolated spells.

TANGO2 spells represent a distinctive early neurological manifestation of TDD that may occur independently of metabolic decompensation. Their recognition can facilitate earlier diagnosis and prompt initiation of preventive supportive strategies.