Distal spinal muscular atrophy type 1

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This article is about a genetic disorder linked to a defect in the 11q13.3 area of chromosome 11. For other conditions with similar name, see Spinal muscular atrophies.
Distal spinal muscular atrophy type 1
Other namesSpinal muscular atrophy with respiratory distress type 1 (SMARD1), Distal hereditary motor neuronopathy type 6 (DHMN6) and Severe infantile axonal neuronopathy with respiratory failure
autosomal recessive manner.
SpecialtyNeurology Edit this on Wikidata

Distal spinal muscular atrophy type 1 (DSMA1), also known as spinal muscular atrophy with respiratory distress type 1 (SMARD1), is a rare

motor neurons in the spinal cord which leads to a generalised progressive atrophy
of body muscles.

The condition is caused by a genetic

autosomal recessive manner. There is no known cure to DSMA1, and research of the disorder is still in early stages due to low incidence and high mortality rates.[1]

Signs and symptoms

Usually, the first respiratory symptoms are shortness of breath (

diaphragmatic paralysis.[2] The symptoms of diaphragmatic paralysis come on very rapidly and without warning, and the patient is often rushed to a hospital where they are placed on a ventilator for respiratory support.[3] Due to the severe nature of diaphragmatic paralysis, the patient eventually needs continuous ventilation support to survive.[2] Continuous ventilation, however, may in itself cause damage to the anatomy of the lungs.[2]

In addition to diaphragmatic paralysis, other issues may arise: as the name suggests, the distal limbs are most affected with symptoms of weakness,

deep tendon reflex is also lost in patients with DSMA1.[3]

Uterine growth retardation and poor

foetal movement have been observed in severe DSMA1 cases.[2]

Causes

Location of the IGHMBP2 gene on chromosome 11, locus 11q13.3

DSMA1 is caused by a genetic mutation in the

mRNA processing.[1] The cellular mechanisms of the mutation, as well as the protein mechanisms disrupted by the mutation, are unknown.[3] IGHMBP2 mutations are usually random mutations which are normally not passed down through generations.[1]

Pathophysiology

The

pressure ulcers, severe constipation, urinary incontinence, and (rarely) reflux nephropathy in the advanced stages of the disease.[3]

Diagnosis

The diagnosis for DSMA1 is usually masked by a diagnosis for a respiratory disorder. In infants, DSMA1 is usually the cause of acute respiratory insufficiency in the first 6 months of life.

respiratory distress should be confirmed as diaphragmatic palsy by fluoroscopy or by electromyography.[citation needed] Although the patient may have a variety of other symptoms, the diaphragmatic palsy confirmed by fluoroscopy or other means is the main criteria for diagnosis. This is usually confirmed with genetic testing looking for mutations in the IGHMBP2 gene.[1] The patient can be misdiagnosed if the respiratory distress is mistaken for a severe respiratory infection or DSMA1 can be mistaken for SMA type 1 because their symptoms are similar, even if they are separate disorders. To avoid misdiagnosis, genetic testing is necessary to confirm the diagnosis of DSMA1.[1]

Classification

DSMA1 was identified and classified as a sub-group of

distal hereditary motor neuropathies, though the latter has been argued to be more correct.[4]

Treatment

There is no known cure to DSMA1, and care is primarily supportive. Patients require respiratory support which may include

immunisations and offered antibiotics to prevent respiratory infections. Maintaining a healthy weight is also important. Patients are at risk of undernutrition and weight loss because of the increased energy spent for breathing.[5] Physical and occupational therapy for the child can be very effective in maintaining muscle strength.[6]

There is no published practice standard for the care in DSMA1, even though the Spinal Muscular Atrophy Standard of Care Committee[further explanation needed] has been trying to come to a consensus on the care standards for DSMA1 patients.[citation needed] The discrepancies in the practitioners’ knowledge, family resources, and differences in patient's culture and/or residency have played a part in the outcome of the patient.[6]

Prognosis

DSMA1 is usually fatal in late infancy or early childhood.[1] The child suffers a progressive degradation of the respiratory system until respiratory failure. There is no consensus on the life expectancy in DSMA1 despite a number of studies being conducted. A small number of patients survive past two years of age but they lack signs of diaphragmatic paralysis or their breathing is dependent on a ventilation system.[1]

Research directions

The disease has only been identified as distinct from SMA recently, so research is still experimental, taking place mostly in animal models. Several therapy pathways have been devised which include

VEGF
).

See also

References

  1. ^
    PMID 22099258
    .
  2. ^
    S2CID 2180011
    .
  3. ^
    S2CID 38923248
    .
  4. S2CID 19966259
    .
  5. PMID 19019300
    .
  6. ^
    S2CID 6478040
    .
  7. PMID 26601156
    .

Further reading

External links
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