DiGeorge Syndrome: the future of stem cell therapy for the genetic primary immunodeficiency disease

by Wideacademy - Updated 15 April, 2018

  • Bone Marrow
  • Stem Cell Transplant
  • Immunodeficiency
  • Thymus

What is DiGeorge Syndrome?

DiGeorge syndrome is a genetic primary immunodeficiency disease caused by the deletion of some genes on chromosome 22, affecting around one in every 5,000 babies.

The outcome for patients can be vastly different depending on which genes are missing.

Although DiGeorge is an inherited disorder (if one parent has DiGeorge there is a 50% chance of passing it onto a child), more than 90% of cases are due to spontaneous mutations — which means there is no family history.

In some cases the symptoms of DiGeorge syndrome are minimal and a patient may not be diagnosed until they have a child with the signs and symptoms

Symptoms of DiGeorge syndrome are sometimes summarised by doctors using the mnemonic “Catch 22”:

  • cardiac abnormalities, such as a hole in the heart, or tetralogy of Fallot
  • abnormal facial features, include a small jaw, long face, broad nasal bridge
  • thymus absence or smallness, which can result in high susceptibility to infection
  • cleft palate and/or lip
  • hypocalcaemia or hypoparathyroidism, low blood calcium levels due to decreased parathyroid hormone

Additional features might include learning difficulties, feeding disorders, neurological conditions.

Only very small numbers of people have complete DiGeorge syndrome and genetic testing is needed to verify a diagnosis.

How is DiGeorge syndrome treated?

There is no definitive cure for DiGeorge Syndrome. However, there are treatments for the different problems the syndrome can cause.

Heart defects can often be treated surgically, as can cleft palate/lip.

Low calcium levels can be treated with supplements, intravenously in extreme cases. Low calcium can cause muscle tetany, involuntary muscle spasms.

Infections will be treated with antibiotics and anti-viral drugs.

Thymus transplantation is sometimes a treatment option. However, only patients with no thymus or T-cell production are eligible, as existing T-cells would attack and reject a transplant.

Growth Hormone has been shown to enhance thymus recovery in several clinical trials. Interleukin-22 is a protein used to treat reduced thymus function and may be useful in DiGeorge syndrome.

The earlier the DiGeorge Syndrome is diagnosed, the better the treatment options for the patient will be.

This is especially true for paediatric patients and those with immune problems. It is important to identify DiGeorge before blood transfusions or live vaccines are given.

Supportive therapies like physiotherapy and speech therapy often form a part of treatment.

Because the associated symptoms of DiGeorge Syndrome are so varied the prognosis can also vary widely. Many people with the disease who reach adulthood live long, independent lives.

How can stem cells help?

A haemopoietic stem cell transplant can treat the immunodeficiency associated with DiGeorge Syndrome.

DiGeorge patients with the complete chromosome 22 deletion have very few T-cells in their peripheral blood so require a thymic transplant or a haemopoietic stem cell transplant.

A small percentage may have a complete absence of T-cells (approximately 1%-2%). This is referred to as ‘complete’ DiGeorge Syndrome and is a form of Severe Combined Immune Deficiency (SCID).

A bone marrow transplant, allowing the transfer of mature T-cells, has been proven to be successful for patients with complete DiGeorge Syndrome. This approach is a useful alternative to a thymic transplant, which may not be available to all patients.

Survival rate post bone marrow transplant for patients with complete DiGeorge Syndrome (using a matched sibling donor) is 75%, which is equally successful as the survival rate for a thymic transplant.

The positive effects in terms of over all health and immune system improvement were also found to be long-lasting following a stem cell transplant.

However, a stem cell transplant is a major procedure and it usually requires a highly toxic chemotherapy and finding a compatible donor can be difficult. It also carries the risk of Graft-versus-Host Disease, where the donor cells attack the recipient.

Advances in diagnostic techniques and genetic technology, improved treatments and better medications mean that stem cell transplants are improving and are increasingly available to patients.

The Washington University School of Medicine is conducting a study to assess the best protocol for patients with primary immunodeficiency disorders such as DiGeorge syndrome.

The researchers anticipate that a reduced intensity immunosuppressive preparatory regime will allow engraftment of allogeneic haemopoietic stem cells, with a reduced risk of GvHD.

The future in science


As the thymus gland is so important to the body’s immune system scientists are exploring ways in which the thymus can be grown in the laboratory for transplant or repaired using stem cells.

The thymus is seen as the “university” of the immune system, because it is where T-cells go to learn how to fight infection. T-cells (a sub-type of white blood cells) which are exposed to infection remember the microbes they have been exposed to in order to fight them again later.

Experiments on mice have shown that when thymus progenitor cells (stem cells which are thymus specific) are injected into a mouse which is missing a thymus, the thymus progenitor cells can go on to make a fully functional thymus gland in the recipient.

Ageing causes the thymus to reduce in size and some medical procedures, such as chemotherapy, can reduce the function of the thymus.

Even if it were to become possible to grow a thymus for transplant, thymus transplant is a complicated procedure. It is currently available (using a donor thymus) in only a few medical centres, such as the Duke University’s Medical Center in the USA.

Cleft Palate

Doctors from Maimonides University in Buenos Aires, Argentina were the first to successfully treat a cleft lip and cleft palate using stem cells to assist in bone regeneration.

Doctors Guillermo Trigo and Gustavo Moviglia used stem cells taken from cord blood to generate bone in newborn infants.

The stem cell treatment is used in addition to multiple surgeries. It has so far only been performed on newborns.