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Cartilage-Hair Hypoplasia and treatment using stem cell therapy

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What is Cartilage-Hair Hypoplasia?

Cartilage-Hair Hypoplasia is a rare, genetic disease characterised by the very light, fine hair of those with the disease.

Typically, it results in short stature (dwarfism), skeletal deformities and a weak immune system.

The light, fine hair characteristic of the disease has no pigment and complete primary alopecia (severe hair loss) affects 15% of people with the condition.

Symptoms include:

  • short limb dwarfism
  • fine, sparse hair and eyebrows
  • skeletal and spinal abnormalities
  • low levels of white blood cells
  • anaemia

Cartilage-Hair Hypoplasia is inherited autosomal recessively. This means both parents are carriers of the disease, although normally they do not show any signs of it themselves.

In rare cases, it can be inherited by uniparental disomy, which is when a child inherits two copies of a chromosome from only one parent, rather than one copy from each parent.

Cartilage-Hair Hypoplasia is most often seen in Amish or Finnish populations. It is affects males and females equally.

The disease is caused by a gene mutation on the short arm of chromosome 9.

Immunodeficiency is seen in 86% of people with the disease, ranging from mild to severe and, in the worst cases, severe combined immunodeficiency, which leaves the body open to recurrent life-threatening infection.

Complications of Cartilage-Hair Hypoplasia include:

  • susceptibility to infection
  • autoimmune diseases
  • blood cancers, such as leukaemia
  • immune system cancers, such as lymphoma
  • skin cancers
  • gastrointestinal problems, such as celiac disease or Hirschsprung’s disease (an inability to digest nutrients)

How is Cartilage-Hair Hypoplasia treated?

For Cartilage-Hair Hypoplasia patients who have related immune system deficiencies, treatment involves antibiotics for infections, vaccinations and immunoglobulin replacement therapy (an injection of donated blood plasma containing antibodies).

In cases of severe combined immunodeficiency, a transplant of donated blood-forming (haemopoietic) stem cells can be an option.

Treatment often relates to secondary complications that Cartilage-Hair Hypoplasia patients are susceptible to, such as cancers and anaemia. The most commonly seen cancers are:

  • non-Hodgkin’s lymphoma
  • squamous cell carcinoma
  • leukaemia
  • Hodgkin’s lymphoma

Anaemia (low levels of red blood cells leading to complications such as fatigue, heart palpitations and pallor) is seen in approximately 80% of sufferers, although, this usually resolves itself in childhood.

In more severe cases treatment includes blood transfusions and bone marrow transplants.

How can stem cells help?

In some cases, Cartilage-Hair Hypoplasia patients with severe combined immunodeficiency (SCID) may be treated with a blood-forming (haemopoietic) stem cell transplant.

A retrospective survey by the European Bone Marrow Transplant group in 2010, reported on sixteen Cartilage-Hair Hypoplasia patients with immunodeficiency, who underwent haemopoietic stem cell transplants. 63% of these patients were long-term survivors with a median follow up of seven years.

This survival rate rose to 80% for patients who had received transplants from HLA (human leukocyte antigen) matched donors — that is, a donor with closely similar markers on their cells. Normally a match is found between close family members, but donors can be unrelated. The closer the HLA match, the greater chance a transplant will be successful.

There is not enough data, particularly long-term data, for a broad sample of patients but the 2010 study does provide an indication that haemopoietic stem cell transplants can be used in certain cases. The study showed that for immune system function improved and autoimmune issues were resolved in all sixteen patients.

Researchers concluded that stem cell transplants should be considered for patients with severe immunodeficiency, recurrent infections and autoimmune indications, before they develop severe infections or organ damage — these are factors which might jeopardise the success of a transplant, and with it, potential quality of life.

However, procedures are only recommended provided there is a good donor match available as patients with severe combined immunodeficiency disorder are more susceptible to graft versus host disease, where the donated cells attack the host.

Further investigation is underway into whether haploidentical transplants should be considered for Cartilage-Hair Hypoplasia patients. A related haploidentical donor is usually a 50% match to the recipient, most likely a parent, sibling or cousin. The advantage of this is that it increases the chance of finding a donor as almost everyone has at least one haploidentical relative.

Also, relatives are usually prepared to donate stem cells more quickly than unrelated donors, which means treatment can be administered before further complications arise, such as severe infections or organ damage. However, the downside is that a 50% match carries a greater risk of graft failure or rejection than an HLA match.

Studies are also being done into whether transplants of donated cord blood could be an alternative for patients who lack a matched donor.

More research is necessary before we can understand exactly which patients with Cartilage-Hair Hypoplasia would benefit from stem cell transplants.

Gene therapy

A recent clinical trial by St Jude’s Children’s Research Hospital, the results of which were published in January 2018, showed promising early evidence for patients affected by severe combined immunodeficiency.

Children with “Bubble Boy” syndrome underwent a bone marrow transplant, but in addition, were treated using re-engineered haemopoietic stem cells, to correct the gene mutation that caused their disease.

Bubble Boy syndrome is a severe combined immunodeficiency disease, in which patients have no immune system and are unable to produce T-cells, B-cells or natural killer cells. Patients usually die before the age of two.

Four months post-trial, four out of five patients had functioning immune systems for the first time.

This new approach offers hope for other genetic diseases that can involve or lead to severe combined immunodeficiency diseases, such as Cartilage-Hair Hypoplasia.

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