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
Image credits – halinaking.co.uk
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
Image credits- bethematch.org

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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Pancreatic Cancer and genetics


Among the other lesser known types of cancers is pancreatic cancer. It is found in 1 per 100,000 people every year as opposed to the 80 cases per 100,000 people diagnosed by breast cancer which is one the most common cancer types in women.

Out of 232,000 people diagnosed with pancreatic cancer in 2002, 227,000 died by 2010, around the world. It is a fast growing and aggressive disease in which the death occurs within five years of the disease diagnosis.

Compared to the West, pancreatic cancer is less common in India, however, in the last couple of years, the rate of cancer cases has gone up. Almost all the cases diagnosed are in the last stage and chances of survival are zero. This cancer is usually found in old-age people.

Image credits -diseasesdata.com
Image credits -diseasesdata.com

Symptoms

By the time cancer is large, it is already grown outside the pancreas and then the symptoms start showing Cancer tumor is generally located on the head of pancreas – an organ that breaks down the food. So the cancer at the head causes symptoms such as jaundice, weight loss, itching, nausea,vomiting, dark urine, back pain, and abdominal pain. Pancreatic cancer in the tail or body of the pancreas generally causes belly and/or back pain and weight loss. Usually, cancers in head of the pancreas show symptoms earlier than the cancers in body or tail.

Pancreatic cancers are of two types – adenocarcinoma and neuroendocrine tumor. Steve Jobs was affected by neuroendocrine tumor – a rare form that is reported in just 5% of people diagnosed with pancreatic cancer.

Pancreatic cancer is diagnosed at a later stage in 89-90 percent cases and in such cases the patient can survive only for18-24 months.

Genetic causes of pancreatic cancer

Inheritance of cancer is one of the causes of pancreatic cancer. Inherited gene mutations are generally passed from parent to child. These mutated genes cause around 10% of pancreatic cancers along with other cancers. Familial pancreatitis is caused by mutations in the gene PRSS1. These mutations and risk factors can be identified using genetic testings like Hereditary Cancer Screening.

DNA mutations in cancer genes often occur after you are born. Most of these cancer causing mutations are after birth rather than being inherited. These acquired mutations sometimes result from exposure to cancer-causing chemicals. E.g. those found in tobacco smoke.

The risk factors like changes in the genes that cause cancer causing syndromes can be recognised by genetic testing.

Surgery, chemotherapy, radiation, and anticancer drugs are some of the treatments for pancreatic cancer that may increase the lifespan of the patients.

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Hereditary Prostate Cancer and Genetics


Did you know that in Indian metro cities, prostate cancer is the second leading type of cancer among males and sixth leading cause of cancer deaths worldwide?

It is the second most common cause of cancer and the sixth leading cause of deaths resulting from cancer among men worldwide. The worldwide number of prostate cancer is expected to reach 1.7 million new cases and 5 lakh deaths in next 15 years. The major reason of this phenomenon is the increasing global population.

Between 1971 and 1975, only 21 per cent of patients lived for at least 10 years after diagnosis. In 2010-2011, the figure reached to 84 per cent. Thanks to the advanced treatments, early diagnosis, and availability of path breaking medications.

About Prostate cancer

Prostate cancer has become a major health problem in the industrialized world during the last few decades of the 20th century contributing to around 75% of the registered cases across the globe. Incidence rates of prostate cancer vary by more than 25 fold worldwide, the highest rates being in Australia/New Zealand, Western and Northern Europe, and North America. Rates of prostate cancer are low in Asian and North African countries, however, the number is increasing in developing countries like India. Out of total diagnosed cases, 75 percent of cases are of men over 75 years of age.

Genes and prostate cancer

One of the causes of prostate cancer is genetic make-up of an individual. Around 10 percent of all prostate cancers are present in families. A recent study throws more light on this topic and explores the various factors involved in prostate cancer. Researchers at the National Institutes of Health identified a gene common in families with a history of prostate cancer. In this study, approximately 100 families with a strong family history of the disease were screened and found that mutations in the HPC-1 gene may lead to develop prostate cancer.

Hereditary Cancer Screening

Genetic screening identifies the gene mutations and the risk of the genetic disorders and many other diseases in an individual, if any. Next Generation Sequencing (NGS) platforms enable us to examine the genetic mutations in members of families with high incidence of cancer. Thus it becomes easy to take measures accordingly that will prevent the cancer as well as improve the life quality of the person, if cancer is present.

Men with BRCA 2 mutation have increased risk of prostate and breast cancer.

Risk reduction options

There are many causes of Prostate cancer out if which genetics is one. Obesity and diet high in animal fats is also attributed to this cancer. However, this type of cancer is often completely curable if diagnosed on time and treated accordingly. There are many treatment options available nowadays for e.g.-  radiation therapy, surgery, hormone therapy, chemotherapy, and immunotherapy. It also requires nutrition and lifestyle changes.

Better screening provides early and better diagnosis of the cancer, helping patient for a better life using correct treatments. Screening helps to identify the future risks hence, it’s advised that men should undergo regular check ups for prostate cancer.

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