Transport And Golgi Organization 2 Homolog - TANGO2

 

 

Transport and organization Golgi homolog 2 (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein encoded in humans by the TANGO2 gene .

 

The function of this protein is not currently known.

 

The C22orf25 gene is located on the long arm (q) of chromosome 22 in region 1 , band 1 and subband 2 (22q11.21) starting at 20,008,631 base pairs and ending at 20,053,447 base pairs .

 

The broad phenotypes arise from different variants of the Tango2 gene including various deletions of not only disease genes but also other unidentified genes.

 

 

People affected by Tango2 disease experience acute episodes called metabolic encephalomyopathic crises , the frequency and severity of which vary:

 

These episodes can be triggered, often by a previous infection or by not eating for a prolonged period (fasting).

Irregular heart rhythms (arrhythmias), breakdown of muscle tissue (rhabdomyolysis), and other complications can occur during an episode.

 

Metabolic crisis:

This may include hypoglycemia, hyperlactacidemia, and mild hyperammonemia.

Urinary organic acids may show marked ketoacidosis and lactic acidosis.

Metabolic abnormalities usually normalize after the metabolic crisis, although some individuals continue to have mildly elevated creatine phosphokinase (CPK) levels.

 

Rhabdomyolysis:   (Myolysis page)

The majority of individuals have intermittent acute episodes of rhabdomyolysis.

It can vary from deep muscle weakness, ataxia and/or disorientation to a comatose state.

 

Cardiac arrhythmias:

During acute illness, transient changes in the electrocardiogram (ECG) may be observed, most often prolongation of the QT interval.

Recurrent ventricular tachycardia (VT) or life-threatening torsades de pointes may occur primarily during periods of acute metabolic crisis resulting in hemodynamic instability.

In this Tango2 disease, there is heterogeneity in people's heart involvement.

Metabolic encephalopathy:

The term encephalopathy is a general term for brain disease.

Neurological problems, including intellectual disability and delays in reaching developmental milestones, can occur.

 

Metabolic encephalopathy affects individuals very differently in this disease.

MRI can show brain volume loss in some cases but most people have normal brain imaging studies.

 

 

Other signs as well as various symptoms can occur both during and outside of metabolic crises:

 

These signs can appear instantly and are sometimes alleviated by rest (sleep) and nutrition:

 

- Decreased cognitive and/or motor skills.

- Episodic muscular weakness / alternating hemiplegia of childhood.

- Benign paroxysmal torticollis (tilting of the head).

- Poor coordination and unsteady gait.

- Hypertonia / Muscular clonus / Spasticity (muscular rigidity) / Hyperactive reflexes...

- Extreme fatigue leading to myopathic facies: drooling, dizziness, confused speech, swallowing problems, dystonia...

 

- Dysarthria:

A motor language disorder characterized by poor articulation.

 

- Hypothyroidism :

Hypothyroidism has been reported in more than a third of people with TANGO2-related disease.

 

- Eye problems:

Intermittent exotropia (lazy eye) has been observed in most individuals.

Some rather rare cases have been diagnosed with optic atrophy.

 

- Hearing:

Sensorineural hearing loss has been described in rare cases.

 

 

There are no cures for most of these disorders, but research is ongoing to better understand and treat this disease.

Current treatment aims to improve the specific symptoms present in each individual with Tango2 disease as much as possible .

 

 

 

 

 

MEDICAL AND SOCIAL CARE OF TANGO2 DISEASE

 

 

Health establishments:

 

- In G2M reference centers (Hereditary Metabolic Diseases Group),

. in consultation / examinations

. in day or conventional hospitalization

 

If I travel:

. in France : I locate the nearest referral centre. (G2M card)

. in Europe : I seek advice from my referring doctor for suitable places of care.

- Local hospital center,

To be consulted in the event of a medical emergency in accordance with its emergency care protocol

 

. It is better to make yourself known beforehand to your local CH.

. It is important to always have your protocol with you and/or saved on your phone.

. The local hospital must be in close contact with the reference center of the subject with tango2 disease (this facilitates treatment guidelines).

- Pediatrician or attending physician

Reception facilities:

- MDPH

The Departmental Houses for Persons with Disabilities (MDPH) were created by Law No. 2005-102 of February 11, 2005.

The MDPH accompanies people with disabilities and their families from the announcement of the disability and throughout its development.

In each department, the MDPH welcome, inform and advise people with disabilities by granting them rights.
 

- Centers for Early Medico-Social Action (CAMPS) up to the age of 6 years 

 

- Medical and Educational Institute (IME)

These are establishments that receive children and adolescents from 3 years old up to around 20 years old, suffering from an intellectual disability, regardless of the severity of the latter. Depending on the needs of each, young people can be received there in day school (for the day) or in boarding school.

 

- Institute of Motor Education (IEM)

It is a medico-social establishment which offers care for children and adolescents subject to significant motor impairment.

 

- Special Education and Home Care Service  (SESSAD)

It takes care of young people aged 0 to 20 with intellectual or motor impairments and character and behavioral disorders. It follows children with multiple disabilities by providing them with personalized support for children. The same is true for school coaching and school support. 

 

- Local School Inclusion Unit upon notification (ULIS)

It is a device that allows the education of students with disabilities within an ordinary school.

 

- Structures for adults: Specialized reception center (MAS), homes….
 

The supporting doctors in the reception facilities (defined by the MDPH) in no way replace the treating doctor.

 

 

 

MEDICAL AND PARAMEDICAL CARE OF TANGO2 DISEASE

 

 

A multidisciplinary, medical and paramedical team provides care for patients and their families… 

 

This support is organized throughout the hospital course at the request of the families and is part of a comprehensive, multidisciplinary and coordinated care.

 

- REHABILITATION DOCTOR:

Its assessment consists of taking stock of the situation of disability… and ensuring the management of this physical disability.

 

- CARDIOLOGIST:

He specializes in heart or cardiovascular disease.

For the Tango2 disease, he monitors any possible problem by various examinations such as cardiac ultrasound, a control electrocardiogram (ECG), a cardiac holter…

 

- ENDOCRINOLOGIST:

Endocrinology is the medical specialty concerned with hormones, their effects on the functioning of the body - metabolism - and related diseases.

For Tango2 pathology, there may be insufficient production of hormones by the thyroid gland.

These thyroid problems are not common to all patients.

 

- ENT (otolaryngologist):

Otorhinolaryngology treats diseases of the head and neck, and more specifically of the ear (oto), nose (rhino) and throat (larynx). This speciality, commonly called ENT, therefore focuses on hearing, the nose and the sinuses, the throat (mouth, tongue, larynx, pharynx, trachea).

 

- OPHTHALMOLOGIST:

Ophthalmology is the branch of medicine responsible for the treatment of diseases of the eye and its annexes. 

The neurovisual disorders observed in Tango2 subjects can alter reading, spelling, writing, calculations or geometry abilities.

The paramedical professions include all  health professionals   who are dedicated to care and treatment, in close collaboration with doctors.

As part of the management of the Tango2 disease, we can cite a wide range of practitioners for ever more complementarity:

 

 

- PHYSIOTHERAPIST:

Physiotherapy is a paramedical specialty that uses active or passive movements. These indications are both preventive and therapeutic, especially for rehabilitation.

 

- OCCUPATIONAL THERAPIST :

Occupational therapy is a health profession concerned with the assessment, rehabilitation and treatment of people with motor or psychomotor disabilities. The goal is to preserve or develop their independence and autonomy necessary for daily, family and professional life.

 

- ORTHESIST PODO:

A specialist in foot fittings, the pedorthist designs orthopedic shoes and insoles. 

 

- PSYCHOMOTRICIAN:

A psychomotor therapist assesses and treats disorders of psychomotor development.

He works with children or adults who have adjustment difficulties.

 

- SPEECH THERAPIST :

The speech therapist prevents, evaluates and treats deficiencies and disorders of oral and written communication, as well as the disorders associated with them. For this, he uses games or exercises adapted to each patient.

Beyond written and oral language disorders, the speech therapist also rehabilitates neurological disorders, people with deafness, genetic or neurodegenerative diseases...

 

- ORTHOPTIST:

The orthoptist is a specialist in eye rehabilitation and low vision (degradation and/or reduction of visual acuity).

 

- PEDOPSYCHIATRIST:

Child psychiatry is the branch of psychiatry devoted to children, from birth to adulthood. It covers the study, diagnosis, treatment and prevention of psychological disorders that affect them...

 

 

 

 

THE RESEARCH

 

 

In France, there are two associations, "No Myolyse" and "Des Ailes pour l" which directly support the search for a treatment for the Tango2 disease as well as its most serious symptoms such as Rhabdomyolysis.

The fundamental research work in progress is taking place in Paris.

 

Patient associations are essential , both financially and morally, because they push research coordinators, clinicians and project investigators to scramble and move forward.

Institutes and various agencies also fund this research: AFM Téléthon, ANR, Rare Disease Foundation, etc.

A call for projects often requires, at the very least, a patient association to start the research work.

There is also a "Tango2 Research foundation" based in the USA which supports various research projects around the world, including the one in France.

 

 

It is a real team work, being in contact with researchers but also with other associations, doctors or families concerned... to understand the pathophysiology of the Tango2 disease, to participate in the orientation towards new therapeutic perspectives in order to minimize rhabdomyolysis and improve the quality of life of patients, hoping why not one day: a curative treatment.


 


 

We hope for great advances in the near future with high hopes for research work on Tango2 disease!  (news page)

 

TANGO 2