Six-month-old Ishaan (name changed) is administered two insulin shots every day, to keep his blood sugar levels in check. His Mumbai-based parents, who are not diabetics, wonder how their child got the disease. Ishaan’s doctors initially suspected he had type-I diabetes, a condition common in children and young adults, but recently they discovered that a mutation in his gene has resulted in him suffering from a condition called neonatal diabetes mellitus (NDM).
The reported incidence of NDM across the world varies from 1 in 89,000 to 1 in 4 lakh live births and could be higher in communities where consanguineous (blood-related) marriages happen. There are 26 lakh live births in India, but only 181 children are registered at Neonatal Data Registry, which is supported by the Indian Council of Medical Research (ICMR).
“There is no study on NDM prevalence in India, but hospital-based studies show it to be 1 in 125 type-1 diabetes patients,” said Dr V Mohan, chairman and chief diabologist at Dr Mohan's Diabetes Specialities Centre (MDRF), Chennai, which runs India’s only Neonatal Data Registry. “There are no reports on region-specific high incidence of NDM in India and we have been getting cases from all over India uniformly, but it could be higher in families where there is consanguinity.”
While a majority of children detected with NDM have mutations in KCNJ11 and ABCC8 genes, Ishaan’s is the first recorded Indian case of NDM caused by a mutation in PDX1 gene, said his doctor, paediatric endocrinologist Dr Abhishek Kulkarni.
With the discovery of another gene mutation in the Indian population, doctors have called for blood sugar tests in sick new-borns for timely detection of NDM. The identification of the specific gene mutation can also help determine the type of treatment.
“At first, no doctor thinks of testing blood sugars in a sick baby. Just checking the blood sugar levels can be lifesaving, as the child can be started on insulin,” said Dr Kulkarni, adding that genetic testing can help switch patients to oral medications.
The mutation in Ishaan’s PDX1 gene has made his pancreas incapable of secreting insulin, the hormone that keeps blood sugar levels from rising too high or dipping too low. Genes carry a set of instructions for a particular function. Mutations in KCNJ11 or ABCC8 genes also lead to reduced insulin secretion by closing the channel that controls insulin secretion.
Ishaan’s parents are shocked at the diagnosis. “We did not believe the doctors initially. Even they [doctors] suspected that his blood sugars could be high because he was on intravenous fluids,” said his father, a Malad resident, who requested anonymity, as he is worried the child will face the stigma associated with the condition.
Another patient, a four-month-old girl from Karnataka, is under treatment for diabetes caused by mutation in another gene. “We thought diabetes was a disease of the elderly. It took almost a month for doctors to detect diabetes in her case. Doctors have told us she will be insulin dependent all her life,” said her uncle, requesting anonymity. “We have not told anyone outside the family about her diabetes.”
A long-term hospital-based study of 40 children with both NDM and IODM (onset of diabetes at less than one year of age) found one in three infants die prematurely, reported Dr V Mohan and his team in Indian Paediatrics in 2013.
Ishaan’s case was detected because of the increasing accessibility to genetic testing which has helped diagnose and treat many cases of NDM, said paediatricians. “In 80% of the cases, we have found mutation in KCNJ11 and ABCC8 gene causing NDM. Diagnosing a child with NDM is vital as high blood sugar levels at birth could even prove fatal,” said Dr V Mohan. “We have not seen a case of NDM where there is PDX1 gene mutation identified.”
Genetic testing for mutation in India can cost about Rs3,000 for a gene. About 23 genes are known to have mutations that can lead to NDM, said doctors, adding that children detected with diabetes within the first six months of birth are most likely to have NDM and not type-I diabetes.
Experts said it is also vital to know the gene mutation responsible for the cause or else the children may remain dependent on insulin injections for life. “We have six children, of whom the eldest is a five-year-old boy who is on oral medicines for NDM. They are doing better compared to the period when they were on insulin injections. Depending on the gene mutation, we can put them on oral medication, allowing the pancreas to secrete insulin,” said Dr Vandana Jain, additional professor, department of paediatrics, All India Institute of Medical Sciences, New Delhi.
“Once we identify the mutated genes, the treatment can be fixed. Some children, depending on the gene mutated, can be switched to oral drugs [sulphonylureas],” said Dr Kulkarni, who is currently treating ten infants with the condition. He has been sending blood samples of his patients suspected of having NDM to University of Exeter Medical School, UK, which provides free genetic testing.
University of Exeter Medical School has tested 127 patients from India for genetic mutation in diabetes. “Around one-third of the patients we have tested from India have those mutations that are likely to respond to oral medication. The lower reported incidence in India could be a combination of non-reported cases and babies who do not survive,” said Sian Ellard, head of molecular genetics, Royal Devon & Exeter NHS Foundation Trust and Professor of Human Molecular Genetics.
For Ishaan’s family, it is not just the stigma of diabetes that is worrying, but also the soaring cost of treatment. The insulin injections, blood glucose monitoring strips and visits to the doctor cost anywhere between Rs 4,000 to Rs 6,000 every month, said his father.
(With inputs from Sanchita Sharma, New Delhi)
TWO TYPES OF NEONATAL DIABETES
* There are two types of neonatal diabetes mellitus (NDM) – transient and permanent
* Transient NDM doesn’t last forever and is usually cured before children turn a year old. But it can recur later on in life, when he/she reaches puberty
* Permanent NDM lasts for life, with the patient requiring oral medication, or insulin, to control blood sugar levels.