7-Month-Old Baby Diagnosed With Rare Genetic Disorder BENTA Disease: All About The Condition

Friday, January 28, 2022, 0:01

As per the latest news, a seven-month-old baby named Vijayendra from Bengaluru (Karnataka) is suffering from a rare genetic disorder BENTA disease. Medical experts who were treating the child have claimed that to date, only 14 people worldwide, including Vijayendra, have the condition and a blood stem cell transplant can help save the life of the child. Also, the child has been diagnosed at an early stage.

A 7-Month-Old Bengaluru Baby Diagnosed With Rare Genetic Disorder BENTA Disease: All About The Condition

The Bengaluru based non-profit organisation DKMS BMST Foundation India is in search of a matching donor. Reports say that only around 0.04 per cent of people in India have registered as potential stem cell donors.

In this article, we will discuss details on BENTA disease. Take a look.

What Is BENTA disease?

BENTA disease is defined as a rare genetic disorder of the immune system. The word BENTA means "B-cell expansion with NF-jB and T-cell anergy". [1]

B-cell: Also known as B lymphocytes, these immune cells mature in the bone marrow.

Expansion: It means that the B cells are in increased amounts than normal.

NF-jB: It refers to a protein complex that regulated genes that are responsible for adaptive and innate immune responses.

T-cell: Also known as T-lymphocytes, these immune cells are produced by the thymus gland.

Anergy: It means "less than normal" immune reaction.

To mention, both B and T cells are parts of the immune system and works together in identifying and damaging pathogen entering our body, along with boosting immunity.

Causes Of BENTA disease

BENTA disease is caused by the gain-of-function mutation in the gene CARD11. The CARD11 gene is the gene that provides instructions for the manufacture of proteins that are responsible for the function of the B and T-cells or say, the immune cells.

Also, gain-of-function mutation means a new or enhanced activity on a protein complex of genes, unlike the loss-of-function mutation that involves poor and nonfunctional protein.

BENTA disease is caused by at least four mutations in the CARD11 gene type, causing the excess production of B-cells. The mutation causes constant NF-jB signalling and always keeps the B-cell production turned on, leading to its excess production.

These abnormal cells do not respond well in fighting against the infection and thus, increase the risk of infection. [2]

BENTA Disease And Genetics

BENTA disease is a genetic disease of autosomal dominant manner. A child receives two copies of the gene, one from each parent. If any of the parents have an abnormal CARD11 gene and this gene passes to any of the children, he/she will develop the BENTA disease.

Patients with BENTA disease often have relatives with the same condition to the side of the family with the CARD11 mutation.

Children are at 50 per cent risk of inheriting the condition if any of the parents have this mutation. Also, it is not necessary that all the children will receive the mutated gene. Meaning, if a father has the affected gene and has three children, it is not necessary that the mutated gene will pass to all three of them.

Also, in the remaining 50 per cent of cases, the mutation can be de novo and is caused spontaneously due to mutation in the sperm or the egg or in the fertilised egg. People with such a mutation may also pass the mutated gene to their children.

Symptoms Of BENTA disease

Children with disorders like lymphadenopathy (enlarged lymph nodes) and splenomegaly (enlarged spleen) usually show symptoms during early childhood. According to a study, patients with BENTA disease may present similar symptoms to the aforementioned lymph diseases, along with elevated levels of certain types of B-cells and a marginal increase of Double Negative T-cells (DNT) in the body.

Some of the symptoms of BENTA disease may include:

Enlarged spleen
Enlarged lymph nodes
Low immunity making them susceptible to viruses like Epstein-Barr virus (EBV) or BK virus [3]
Recurrent upper respiratory tract infections. [4]
Otitis media, in some cases.

Risk Factors Of BENTA disease

The main risk factor for the development of BENTA disease is a mutated gene.

Complications Of BENTA disease

Experts say that BENTA disease may lead to the risk of certain diseases like:

B-cell cancer
Leukaemia, in some cases

Diagnosis Of BENTA disease

The minimum age at which BENTA disease can be diagnosed is 3-9 months which may range to 36 months. As aforementioned, children mainly with enlarged lymph nodes and spleen and recurrent respiratory distress at an early age is suspected of BENTA disease.

Patients are initially screened for mutation in the gene CARD11 by Sanger sequencing.

Complete blood count tests are suggested to diagnosed BENTA disease. The test shows any alterations in the levels in the immune cells. [5]

Bone marrow aspiration and biopsy are also suggested along with serology and viral PCR for checking infections like hepatitis and Epstein-Barr virus (EBV).

Treatments Of BENTA disease

There's no specific treatment method for BENTA disease as the condition is mainly managed with medications and surgeries.

For example, patients with EBV infection is kept on steroid and drugs like azathioprine and rituximab. Those with ALPS are given Sirolimus (Rapamycin). [6]

As in BENTA disease the immune cells malfunction, there is an increased risk of triggering various conditions, along with the chances of recurrence of those conditions. Therefore, such patients are kept under observation and another management strategy is applied as soon as the first does not respond well.

Surgery is suggested in some cases to remove the enlarged spleen.

Stem Cell Transplant And BENTA Disease

Stem cell transplant or bone marrow transplant is a treatment method in which the bone marrow of a patient is replaced with healthy cells. The treatment is mainly recommended for blood and immune system disorders.

Stem cells are considered to be special human cells with the ability to multiply and develop into different types of cells required by the body. Consider it raw cells from which other cells with specific functions are generated.

Stem cells are found in various body parts, including the bone marrow, which is a spongy tissue found in the centre of some bones like hip and thigh bones. The cells have the capability to develop into red blood cells, white blood cells and blood platelets and perform the respective functions.

As BENTA disease is a condition that affects lymphocytes or white blood cells, stem cell transplant can be an effective treatment method for the condition.

Replacing the unhealthy white blood cells with healthy cells can help maintain B and T cells levels in the body and treat or manage the condition well.