Thymic aplasia

Definitions & Key takeaways

Thymic hypoplasia is a condition in which the thymus is underdeveloped or involuted, leading to a reduced number of T cells. There are two main causes of thymic hypoplasia, DiGeorge syndrome, and Ataxia-telangiectasia syndrome, both cause a reduction of thymic cells. In DiGeorge syndrome the parathyroid glands are underdeveloped, this results in less parathyroid hormones which results in hypocalcemia. On the other hand, in Ataxia-telangiectasia syndrome, the parathyroid glands develop normally, this results in normal levels of parathyroid hormones which results in normal levels of calcium in the blood.

Symptoms of thymic hypoplasia include repeated infections because of a weakened immune system due to a T cell deficiency. In DiGeorge syndrome, there are also symptoms caused by hypocalcemia such as osteoporosis and tetany, or involuntary contraction of muscles. Other symptoms associated with this disorder are congenital cardiac defects like tetralogy of Fallot, cleft palate, and learning disabilities. In ataxia telangiectasia, there can also be symptoms like ataxia which is a problem with muscle coordination, telangiectasia, which are dilated blood vessels in the skin and eye, and an increased risk of cancer.

Treatment is focused on managing symptoms and preventing complications, and can include antibiotics and antiviral medications to prevent infections, nutritional support to promote growth, and surgical interventions for cardiac abnormalities or cleft palate.

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Introduction0:00–0:21

In thymic hypoplasia, thymic refers to the thymus which is an immune organ that sits between the lungs, hypo- refers to under, and -plasia refers to development.
So, thymic hypoplasia is a condition where the thymus is underdeveloped and has a reduced number of cells. By week 4 of development, the embryo takes on a more recognizably “human” form—but to be honest, it still looks more like a shrimp than a baby.

Physiology0:21–2:07

At the head end of this little shrimp-like creature, a set of structures called the pharyngeal apparatus begins to develop, consisting of pharyngeal arches, clefts, and pouches.
The components of the pharyngeal apparatus develop into various head and neck structures, and sometimes multiple arches join together to give rise to a single structure.
Now, the epithelial tissue of the embryo’s third and fourth pouch turns into the inferior parathyroid glands as well as the superior parathyroid glands, while the epithelial tissue that lines the ventral region of the third pouch forms the thymus.
Both glands then go on to break off from the pharyngeal wall and eventually attach to the posterior side of the thyroid.
The thymus now free, migrates down the middle of the pharynx, until it ends up in its final position in the front of the thorax where it fuses with its counterpart from the opposite side.
During childhood, the thymus occupies considerable room behind the sternum, in a part of the chest known as the mediastinum, a space in the chest between the lungs that also contains the heart.
But when people become older, it atrophies and is replaced by fatty tissue. It's here in the thymus, where certain immune cells from the bone marrow mature into T lymphocytes or T cells, where the T stands for Thymus.
Once mature, these T cells help defend the body against infections by activating other cells of the immune system as well as checking the body’s cells for viral infection or abnormalities like cancer.

Thymic hypoplasia in DiGeorge syndrome2:07–3:16

In thymic hypoplasia, a small portion of chromosome 22 is deleted in a condition known as DiGeorge syndrome or 22q11.2 deletion syndrome.
On chromosome 22, there’s a gene called TBX1 that controls the development of the 3rd and 4th pharyngeal pouch during the prenatal period.
So, when there’s a 22q11.2 deletion, there’s no TBX1 gene, and the thymus and parathyroid glands ends up underdeveloped.
In thymic hypoplasia, the immature T cells from the bone marrow don’t have a place to go to mature, and so these people often have a deficiency in mature T cells.
The parathyroid glands also remains underdeveloped. Normally it secretes parathyroid hormone which promotes the absorption of calcium in the intestines as well as kidneys while breaking down bones to release more calcium into the blood.
But when the parathyroid glands are underdeveloped, there’s less parathyroid hormone which results in hypocalcemia. Thymic hypoplasia also happens in people with ataxia-telangiectasia syndrome, and there It's caused by a defect in the ATM gene, or Ataxia-Telangiectasia Mutated gene, found on chromosome 11.

Thymic hypoplasia in Ataxia-Telangiectasia3:16–4:39

The ATM gene encodes a protein whose job is to recognize DNA damage and activate proteins to fix the damage. Another function of the gene is to maintain the distal portion of our chromosomes called telomeres.
These telomeres protect the ends of the chromosome from degeneration, and when the telomere becomes too short, the chromosome can no longer become replicated.
In ataxia-telangiectasia syndrome, rapidly dividing cells like thymic cells, die prematurely, which leads the thymus to atrophy.
Motor neurons in the cerebellum also die prematurely, leading to uncoordinated muscle movement called ataxia. Just like in DiGeorge syndrome, T cells don’t have a place to mature, and so these people become deficient in mature T cells, making them susceptible to infections.
In ataxia-telangiectasia syndrome, unlike DiGeorge syndrome, the parathyroid glands develop normally, and secrete normal levels of parathyroid hormone which results in normal calcium levels in the blood.

Symptoms4:39–5:25

Early symptoms of thymic hypoplasia are repeated infections due to a T cell deficiency which results in a weakened the immune system.
In DiGeorge syndrome there are also symptoms caused by hypocalcemia which include osteoporosis and tetany or involuntary contraction of muscles.
Other symptom associated with this disorder are congenital cardiac defects like tetralogy of Fallot, cleft palate, and learning disabilities.
In ataxia telangiectasia, there can also be symptoms like ataxia which is a problem with muscle coordination, telangiectasia, which are dilated blood vessels in the skin and eye, and an increased risk of cancer.

Diagnosis5:25–5:57

Diagnosing thymic hypoplasia often begins with genetic testing, which can help identify if it’s DiGeorge syndrome or ataxia-telangiectasia syndrome.
And certain blood tests looking for T cell numbers and function can help determine the cause of recurrent infections. Also, calcium levels in the blood may hint at the two conditions associated with thymic hypoplasia.
In DiGeorge syndrome, there is hypocalcemia while in ataxia telangiectasia there's normal levels of calcium or eucalcemia.

Treatment5:57–6:08

Antibiotics may be used to treat infections from thymic hypoplasia. Surgery might be required for more severe cases though, like a thymus transplant.
All right, as a quick recap, thymic hypoplasia is a condition where the thymus is underdeveloped leading to a reduced number of T cells.

Review6:08–7:31

There are two main causes of thymic hypoplasia, DiGeorge syndrome, and Ataxia-telangiectasia syndrome, both of which cause a reduction of thymic cells.
In DiGeorge syndrome the parathyroid glands are underdeveloped, this results in less parathyroid hormones which results in hypocalcemia.
On the other hand, in Ataxia-telangiectasia syndrome, the parathyroid glands develop normally, this results in normal levels of parathyroid hormones which results in normal levels of calcium in the blood.