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

By Wideacademy - 10.01.2018


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 specific treatment for DiGeorge syndrome, but a there are treatments for the different pathologies which 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.

Thymus deficiencies result in immunodeficiency. DiGeorge syndrome patients are therefore predisposed to more frequent and extensive infections, which are mostly 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.

Can stem cells be used to treat DiGeorge syndrome?

Bone marrow transplants can be used to treat DiGeorge patients born without a thymus gland. The stem cells for this procedure are obtained from either donor bone marrow or donor cord blood.

The first bone marrow transplant on a DiGeorge sufferer took place 30 years ago at Mattel Children’s Hospital UCLA.

A baby girl with severe immune deficiency had a successful bone marrow transplant and when doctors caught up with her 8 years later her immune system had continued to do well.

UCLA researchers began a study of this child and nine other DiGeorge bone marrow transplant cases worldwide. In 2007 they found that survival rates with bone marrow transplants were 75 per cent — similar to the survival rates in DiGeorge patients who had thymus transplants.

What is the future of treatment for DiGeorge using stem cells?


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.

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.