SIGNS

& SYMPTOMS

Primary Symptoms

 

Metabolic Crisis
Rhabdomyolysis
  • Majority of individuals present with intermittent acute episodes of rhabdomyolysis.
  • Dark urine due to myoglobinuria and profound lower-extremity weakness can develop.
  • Acute renal tubular damage due to myoglobinuria can result in acute kidney injury and renal failure.
  • Creatine phosphokinase (CPK) can be significantly elevated in some individuals (>200,000 U/l).
  • Elevated aldolase and transaminases can also occur
  • For French-speaking families, visit No Myolyse to learn more about efforts underway in France to combat rhabdomyolysis
Variable Acute Presentation
  • Acute presentation can vary from profound muscle weakness, ataxia, and/or disorientation to a comatose state
Cardiac Arrhythmias

Other Important Symptoms Contributing to Diagnosis

Intellectual Disability
  • Intellectual disability/developmental delay is present in almost all individuals with varying severity
Regression
  • Loss of motor and cognitive skills
Poor Coordination and Unsteady Gait
  • Poor coordination, unsteady gait, or clumsiness is frequently reported in individuals who are walking even prior to the first episode of metabolic crisis or rhabdomyolysis
Increased Tone
  • Muscles are tight and tense even at rest with reduced capacity to stretch.
  • Can lead to spasticity and rigidity
Episodic Muscle Weakness
  • Unable to sit without falling
  • Difficulty with grasping items/toys
  • SEE VIDEOS
Benign Paroxysmal Torticollis (BPT)
  • BPT typically manifests as a head tilt to one side for a few hours or days. It may not be affected by sleep. Spells can last as little as 10 minutes or as long as 2 months.
  • SEE VIDEOS
Hyperreflexia
  • Overactive reflexes
Clonus
  • A series of involuntary, rhythmic, muscular contractions and relaxations
  • SEE VIDEOS
Dysarthria
  • A motor speech disorder characterized by poor articulation
Myopathic facies
  • Facial appearance with bilateral ptosis (droopy eyes) and inability to elevate the corners of the mouth due to muscle weakness
Seizures
  • Seizures are observed outside of crises in more than 75% of individuals including generalized myoclonic seizure and atonic seizures.
  • Seizures are generally responsive to antiepileptic medications
Brain Imaging Abnormalities
  • MRI may show cerebral volume loss.
  • Some affected individuals had prominent lateral ventricles, with progressive brain atrophy.
  • Some individuals have normal brain imaging studies.
Hypothyroidism
  • Hypothyroidism has been reported in more than one third of individuals with TANGO2-related illness.
  • Elevated serum thyroid stimulating hormone (TSH) and low free T4
Ophthalmology
  • Intermittent exotropia (lazy eye) has been observed in most individuals.
  • Rare individuals have been diagnosed with optic atrophy.
Other Episodic (non-seizure) Symptoms
  • can include torticollis, instant onset fatigue, loss of muscle control, weakness, dizziness/balance issues, garbled speech, drooling, swallowing issues, dystonia, and/or clonus
  • Presentation and duration can vary with each episode
  • They can be instant onset and are sometimes alleviated by sleep.
  • SEE VIDEOS
Hearing Loss
  • Sensorineural hearing loss has been described in rare instances.
(Reference: TANGO2-Related Metabolic Encephalopathy and Arrhythmias  – GeneReviews – Jan 2018)

Early, non-acute signs of TANGO2-related disease may include a combination of the following symptoms: