A 10- year-old child has been diagnosed with Juvenile diabetes mellitus (type 1 diabetes mellitus). This is a disorder of carbohydrate metabolism caused by insulin deficiency. The disease is often preceded by viral infection with inflammation of the beta cells of pancreas, but also exhibits genetic predisposition with a 40-50% concordance rate in monozygotic twins and clustering in families. Type 1 diabetes mellitus may be best described as a
A. Sex linked disorder
B. Congenital disorder
C. Sporadic disorder
D. Multifactorial disorder
E. Mendelian disorder
Answer- The correct answer is- D, Multifactorial disorder.
Many common diseases are caused by a combination of environmental factors and genetic factors, and are described as multifactorial diseases. Examples include- Diabetes mellitus, Heart attack, Schizophrenia, alcoholism etc.
Approximately one-third of the disease susceptibility of type 1 diabetes mellitus is due to genes and two-thirds due to environmental factors. (Figure)
The global incidence of type 1 diabetes is increasing (approximately 3% each year).This form of diabetes is immune-mediated in over 90% of cases and idiopathic in less than 10%.
Which environmental factor is responsible for the increased risk is not known. There have been a number of different hypotheses including infections with certain viruses (rubella, Coxsackie B4) and consumption of cow’s milk. None of these factors has so far been confirmed as the culprit.
The autoimmune destruction of pancreatic β-cells leads to a deficiency of insulin secretion. It is this loss of insulin secretion (figure) that leads to the metabolic derangements associated with IDDM (insulin dependent diabetes mellitus) Less than 10% of subjects have no evidence of pancreatic B cell autoimmunity to explain their insulinopenia and ketoacidosis. This subgroup has been classified as “idiopathic type 1 diabetes” and designated as “type 1B.”
Children of diabetic parents are at increased lifetime risk for developing type 1 diabetes. A child whose mother has type 1 diabetes has a 3% risk of developing the disease and a 6% risk if the child’s father has it. The risk in siblings is related to the number of HLA haplotypes that the sibling shares with the diabetic parent. If one haplotype is shared, the risk is 6% and if two haplotypes are shared, the risk increases to 12–25%. The highest risk is for identical twins, where the concordance rate is 40–50%. This percentage of genetically identical monozygotic twins who share this trait of diabetes mellitus provides a measure of the genetic contribution to the etiology.
As regards other options in the question
- Sex linked disorders predominantly occur in males or females, in contrast to the equal distribution in males and females in type 1 diabetes mellitus.
- Congenital disorders are present at the time of birth, in contrast to type 1 diabetes mellitus which usually presents during childhood.
- Sporadic disorders have no genetic predisposition and do not cluster in families except by chance or through similar environmental exposure.
- Mendelian disorders are completely determined by the genotype of an individual, and exhibit 100 % concordance in identical twins.