Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome
Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome is a rare metabolic and genetic disorder which is caused by mutation in a gene TANGO2. Main signs of this disorder are: Intellectual disability, ataxia, underactive thyroid, and life-threatening episodes of metabolic and cardiac crises, rhabdomyolysis.
The syndrome affects about 1/1 000 000 births, with about 110 cases having been reported worldwide.
Symptoms
Symptoms of this disorder might include:Very frequent:
- Abnormal ECG
- Elevated blood creatine phosphokinase
- Global developmental delay
- Intellectual disability
- Ketone bodies in urine
- Abnormally increased level of blood lactate
- Extrapyramidal signs
- Rhabdomyolysis, acute
- Ataxia
- Irregular heart beat
- Mild hypothyroidism
- Loss of milestones
- Delayed speech and language acquisition
- Delayed walking
- Abnormal liver enzymes
- Gastrointestinal dysmotility
- Generalised brain atrophy
- High blood ammonia levels
- Low blood sugar
- Involuntary muscle contractions
- Increased lactate in body
- Prolonged QT interval
- Seizure
- Lazy eye
- Positive Babinski sign
- Generalised convulsion
- Cortical visual impairment
- Involuntary rhythmic muscular contractions and relaxations
- Swallowing difficulties
- Dystonic movements
- Elevated plasma acylcarnitine levels
- Increased deep tendon reflexes
- Increased muscle tone
- Infantile spasms
- Involuntary, rapid, rhythmic eye movements
- Optic-nerve degeneration
- Stroke
- Supranuclear gaze paralysis
- Decreased size of head
- Sensorineural deafness
Cause
This disorder is caused by a mutation in a gene, TANGO2, which codes for protein Transport and golgi organization 2 homolog, and its located on chromosome 22. According to one study, exons 3-9 are frequently deleted in people of European origin and Hispanic ethnicity, although in Hispanic ethnicity c.460G>A is also frequent.Also, people with 22q11.2DS are at risk of developing this disorder because of hemizygosity.
Pathophysiology
TANGO2 plays role in mitochondrial β-oxidation, consequently in that disease, β-oxidation and ATP levels are reduced. Interestingly TANGO2 also might participate in retrograde ER-Golgi trafficking, consequently this process is slowed down in this disease, and the supplementation of TANGO2 has restored that process.According to one study, TANGO2 also might participate in autophagy process, which might be responsible for rhabdomyolysis in this disease.
Diagnosis
This disorder can be suspected by symptoms, although diagnosis can be confirmed by a genetic testing. Also, diagnosis is usually made after first episode of life-threatening symptoms.Treatment
This disease doesn't have a cure. Although symptom management is available, and this might include:- Supplementation of all B vitamins, such as B5 and B9, because they might alleviate some of the symptoms.
- Levothyroxine for Hypothyroidism
- Supportive treatment for developmental delays
- Antiseizure medication