MODY Diabetes

MODY Testing – Caring For the Younger Generation

It was a misconception until the last few years that diabetes only affects the person after a certain age. However, the studies have shown the onset of diabetes in a younger generation as well.  There are various hereditary forms of diabetes caused due to the mutations in a gene. They are called MODY – Maturity–Onset Diabetes of the Young. It is said that approximately 5% of all diabetes cases are MODY. People of Asian Indian descent may have greater chances of MODY compared to the others.

About MODY

MODY is a group of around 6 different genetic defects that damage response to the insulin. Different types of defects have different symptoms based as well as different therapies.

MODY is caused because of the mutations in an autosomal dominant gene that disrupts the insulin production. Whereas type 1 & type 2 diabetes is a result of multiple factors and genes. Some of these types can be treated or managed with changes in lifestyle, some get benefits from sulfonylureas while others need insulin.

HNF1 – alpha, HNF4 – alpha, HNF1- beta, Glucokinase are some of the types of the MODY Diabetes.

Gene Inheritance- MODY
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There are differences between how the different versions of MODY manifest. But here are some of the traits several forms of MODY have in common:
  1. People with one of the forms of MODY that primarily affect the secretion of insulin in response to a meal may have near-normal fasting blood sugar test readings and very high post-meal blood sugars.
  2. The age of onset of diabetes in at least one form of MODY is significantly younger if it was the mother who passed on the gene; may be because of the exposure to high blood sugars in the womb affects the expression of the MODY gene in the offspring.
  3. It is a myth that MODY only affects people under 25. It may develop at any age up to 55.
  4. Women with MODY are often first diagnosed during a first pregnancy. Though not obese, they develop gestational diabetes very quickly.
  5. People with MODY often are not insulin resistant.
  6. Some versions of MODY respond very well to drugs that stimulate insulin secretion.
  7. In one common form of MODY, fasting blood sugar is normal, but insulin secretion begins to fail as blood sugars go over 144 mg/dl.
  8. People with some forms of MODY often have subtle or more obvious congenital kidney defects and may even have signs of kidney disease before they are diagnosed with diabetes.

A person diagnosed with Type 1 Diabetes might have MODY if:-

  1. They had diagnosed of diabetes before 6 months of age.
  1. They have a parent with a family history of diabetes. (Only 2% to 4% of people with Type 1 have an affected parent).
  1. They have detectable insulin production three years or more than that after the diagnosis.
  1. They have no immune antibodies to their islet cells, especially at diagnosis.

Most of the times, MODY is misdiagnosed as type 1 or type 2 diabetes because there are no distinct symptoms to distinguish MODY from other types of diabetes. This is where genetic testing plays an important role. Genetic test offers definitive diagnosis for the mutations linked to the disorder.

About the MODY test

MODY is caused by mutations in any one of more than 10 genes while over 20 genes have been associated with monogenic neonatal diabetes. Depending on the genes involved, the course of treatment varies.

The genetic test is very simple – It involves collecting either a blood or saliva sample and sending it to a laboratory for testing.  The sample is used to make DNA and gene sequencing is performed.  The order of bases in a person undergoing genetic testing is compared to the correct order for each gene being tested.  Mutation is considered if there is a difference in the pair.  However, not all mutations will actually cause diabetes. Hence, it is very important to check with the expert if results of genetic testing are really the cause of diabetes.

Because of the high level of precision, genetic testing turns to be very helpful for the patients and helpful for their better future.

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HLA Typing and matching

This Is Why HLA Typing Is Very Important For Organ & Tissue Transplants

Nikhil (name changed), a 10 year old boy was diagnosed with Beta Thalassemia Major – a severe form of blood disorder. As the days passed by, his health started deteriorating at a fast pace. However, according to the doctors there was a ray of hope – Neeraj, his 7 year old brother.  His umbilical cord blood was harvested and saved after his birth and that meant Nikhil’s chance of survival. Presently, cell-stem transplant is the only cure for B-Thal major.

To match the compatibility of the donor and the receiver, HLA Typing is necessary. After the typing, the compatibility was matched. After a successful transplant, Nikhil made a recovery and now shows no signs of B-Thal.

About HLA

HLA (human leukocyte antigen) is a protein or marker – found on cells in human body. Immune system uses HLA markers to know which cells belong in our body & which don’t. Its main use is in organ and tissue transplant treatments. It checks if receiver and donor are compatible.

For example, in bone marrow transplant, HLA genes and antigens of donor and the recipient should be same or match closely for a transplant to be successful. Otherwise the donor’s tissue may get attacked or rejected by the recipient’s immune system.

HLA testing and matching
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What is HLA Typing?

A high-resolution typing result is defined as a set of alleles that encode  the  same  protein  sequence  for  the  region  of  the  HLA molecule called the antigen binding site and that exclude alleles that are not expressed as cell-surface proteins.

Every person (except identical twins) has different sets of HLA alleles. Transplanted organs are allografts, in which the donor organ and the recipient are genetically different. Compatibility (matching) of the HLA of the donor and the recipient increases the chance for a successful engraftment. Matching is determined by comparing alleles. Resolution is the level of detail with which an allele is determined. The MHC is a polymorphic locus encoding the HLA genes.

Antigens encoded by the HLA genes are responsible for allograft tissue and organ rejection. Identifying and matching alleles increases the chance of successful organ and tissue transplant. These antigens help the body’s immune system distinguish which cells are “self” and which are “foreign” or “non-self.” Any cells that are recognized as “non-self” can trigger an immune response, including the production of antibodies.

Different kinds of transplants necessitate different levels of matching between donor and intended recipient. This may determine which HLA tests are performed and which HLA genes are tested for.

HLA antigens and their corresponding sequence alleles are determined by serological- and DNA- based methods.

Why is it necessary?

Determination of HLA alleles by DNA typing techniques is necessary for HLA matching of donor and recipient at transplantation, medical research of HLA-related diseases and individual identification including paternity testing.

This testing also includes screening transplant recipients for the presence of antibodies that might target the donated tissue or organ as part of an immune response.

HLA mis­matches found using very sensitive tissue-typing methods — methods known as “high-resolution” typing — can have just as significant an impact on trans­plant outcomes as mis­matches found using “low-resolution” methods.

High-resolution typing is important for ensuring the best possible match between donor and recipient because a match suggested by Low Resolution HLA Typing is generally only 56% accurate.

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Liquid Biopsy and its role in fighting cancer

Wrong diagnosis and wrong medications can lead to fatal results in person’s health. According to September 2014 bulletin of Sample Registration System (SRS), India has an infant mortality rate of 40 per 1,000 live births.Wrong drugs cause 50 deaths out of 1000 patients in India. Most of the times, a regular disease can exaggerate and become fatal because of the wrong diagnosis and medications. Same was the case with Mr. Deshpande (name changed) – which almost took a toll on his life.

When Mr. Deshpande, a 74 year old retired banker started suffering from abdominal pain, weakness, and fatigue, his wife was alarmed because he had always been very careful about his diet and exercise regime. Neither did he miss his regular check-ups. He wanted to lead his retirement exactly the way he had planned. However, all his plans were short lived because of his constant health issues after the retirement.

On the contrary, he also lost his weight drastically. When his wife took him to their GP, he referred them to an expert in the city where he was first diagnosed with adenocarcinoma of colon in November 2013.

After the diagnosis, the doctors suggested surgical resection which would be followed by chemotherapy. Doctors also advised a Positron Emission Tomography (PET) scan. This scanning is basically to check how the tissues and organs in the body are working. A year later,in November 2014, while testing, a mass measuring 2.1 x 1.7 cm was detected in the lung with speculated margins. The doctors assumed it as a metastasis from colon cancer and started with Capecitabine – a chemotherapeutic agent.

After the prescriptions, he was being continuously monitored with PET scans. However, despite of the chemotherapy which was ongoing since a year, the mass was continuously increasing in size.

Doctors were not sure if it was indeed a metastasis of colon cancer, or it was a result of tuberculosis or in a worse case, primary lung carcinoma?

After looking after a varied possibilities and options, he was referred for a liquid biopsy. However, Mr. Deshpande was reluctant because of general perception of the biopsies. He was only relieved when the doctors explained that the procedure is as easy as a simple blood test.

Liquid Biopsy showed mutation burden 4.4 % of total cell free DNA. It was an indication of active primary lung carcinoma. The Liquid Biopsy indicated therapeutic response to targeted anti EGFR therapies such as Afatinib, Gefitinib and Erlotinib.

Here, Gefitinib was prescribed to the patient. This drug is only effective in cancers with mutated and overactive EGFR. It started showing its results and the tumor began to shrink gradually. Repeat PET scan showed reduction in tumor size by 70%. That meant a great success of the accurate diagnosis and correct medications.

Liquid Biopsy after three weeks
Liquid Biopsy after three weeks

Five weeks later, detectable mutation burden in the cell free DNA obtained from plasma was negative. The mutation burden was reduced even more as compared to the previous analysis possibly due to Gefitinib therapy.

Mr. Deshpande is completely hale and hearty now. It’s interesting how one correct step towards the course of treatment can leave a huge impact on patient’s well-being.

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Neurology and pharmacogenetics

Pharmacogenetic analysis for Neurology/Psychiatry

Adverse Drug Reaction (ADR) is one of the most common causes of deaths worldwide. It also causes 50 deaths out of 1000 patients in India. These statistics highlight the importance of correct drugs for the treatment. This is where Pharmacogenetics plays an important role.

What is pharmacogenetics?

Pharmacogenetics is the study of inherited genetic differences in drug metabolism which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.

Why pharmacogenetics?

In a last few years, importance of pharmacogenetics has increased tremendously in medical practice. This testing particularly benefits psychiatric patients as the drugs and medications suggested in the treatments can lead to variety of side-effects. The use of pharmacogenetic screening can help the expert to design psychotropic treatments and make informed decisions which prove to be very useful most of the times.

Many cases and studies have been published in recent times which prove the positive results in the patients. Along with the better outcome, genetic testing also helps to decrease the medical costs. Recently, many studies have been published demonstrating improved patient outcomes and decreased healthcare costs for psychiatric patients who utilize genetic testing.

The very first genotyping test used in psychiatry was Roche’s AmpliChip CYP450 test. It received clearance from FDA in December 2004.

The risk of adverse drug reaction is more in children and adolescents who have metabolic disorders as their system finds it hard to break down the new elements in it.

Pharmacogenetics is important in neurology / psychiatrics because –

  • It gives an insight of patient’s metabolic response
  • Prescribes surer, safer and targeted drug therapy
  • Promotes avoidance of Over-dose/ Under-dose
  • Minimizes Adverse Drug Reaction (ADR)
  • Eliminates trial and error in therapy
  • Offers optimum therapeutic response
  • It’s an affordable and once in a life-time test
  • It protects doctor from medico-legal complications

It is a common belief that high-end medical tests only prescribe equally high-end and expensive treatments. However, it is not the case; pharmacogenetic screening identifies the most effective course of conventional treatments and also suggests equally effective alternate options.

The widespread application and utility of pharmacogenetics in neurology/ psychiatry will only keep increasing along with its knowledge and understanding. With continuous research, it is very vital that medications and drugs will get more narrowed down on the basis of their effectiveness to the patients.

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Legs and pelvis are affected first in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy and Genetics

When Ranjeetha and Rakesh were preparing Anish, their 3 year old for pre-school, they observed that he had difficulty walking and sitting up. They took a primary treatment from their family doctor but as the problem persisted over the year, they were worried and decided to take him to the specialist and Anish was diagnosed with Duchenna Muscular Deficiency (DMD). They were heartbroken with the thought that Anish would have to spend the rest of his life bedridden, or on a wheelchair – totally dependent on others. But very little they knew that their genes were responsible for his condition.

What is DMD?    

Duchenne Muscular Dystrophy is a disorder caused by inherited mutations in genes. It affects protein in Dystrophin (muscle fibres) and causes progressive muscle weakness because of the breakdown and loss of muscle cells. There are around 20 types of muscular dystrophies, but Duchenne type affects only boys, and in rarest of the rare conditions – some girls. The problem here is, the disease is not diagnosed in the infancy, but around the time when child is around 3-5 years of age.  It is named after gentleman from Paris named Dr Duchenne de Boulogne who worked on DMD for the first time in 19th Century.  Even though inherited faulty genes are linked to this gender-specific disease, it can also affect girls in some rare cases through some mutations.

Curvature in spine due to DMD
Curvature in spine due to DMD


It starts with increasing muscle weakness of pelvis and the area below along with a loss of muscle mass. Slowly the weakness spreads to the other parts of the body. In the initial stage, the symptoms include enlarged calf muscles, low endurance, and difficulty in standing & climbing stairs without any help.

In the later stage, muscle tissue gets replaced by fat and tissues caused by wastage. By age of around 10, the patient requires help for walking and fully dependent by the age of 12-13 years. After that, bones develop abnormally and spine curves in an abnormal manner. Eventually it leads to paralysis. It also affects the intellect of the patient but that is not confirmed.

Inheritance of DMD
Inheritance of DMD

Role of genes

This disorder is caused by an X-linked gene. Here, the carriers of mutated genes are mostly mothers. However, in most of the recent cases, it is observed that gene mutation occurs in the boy himself rather than mother being the carrier. In more than 50 percent of the cases the mother is the carrier of the mutated genes. Son and daughter of the carrier have 1:1 chance of being affected by the mutated genes, but the number of affected girls is very less.

Once a boy in the family has been diagnosed with DMD, it is advised to undergo genetic screening for the other members of the family who may be at a risk of being carriers. At DGL, we have ‘Genetic Testing for Duchenne Muscular Dystrophy which identifies the risk of the disorder and also detects the level of mutations. It helps parents of the affected children to take necessary measures.

The average life expectancy for patients afflicted with DMD is around 25, but this varies from person to person. It’s a disease that affects 1 in about 4000 baby boys. The course of treatment changes according to the stage of the disease. Though there are medications available, physiotherapy plays a major role in comforting the patient and improving their life quality.

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