The 2013 Nobel Prize in Physiology or Medicine

 Some genetic diseases are caused by defects in the transport of proteins within cells.  An understanding of the mechanisms involving transport of proteins via vesicles was the research work that led to the 2013 Nobel Prize in Medicine / Physiology. (Read about it).  

Genetic diseases can be caused by single gene abnormalities, chromosomal abnormalities or by a combination of genetic and environmental factors. Abnormalities in genes cause diseases in various ways:

1. Excess production of proteins. An example is the fragile X syndrome which shows itself as learning disability or mental retardation and autistic behaviour. This is caused by excess production of a protein that is used in synapses of the brain.

2. Insufficient production of proteins. An example is the group of diseases called glycogen storage disorders which can present with hypoglycaemia, hepatomegaly and/or muscle weakness.

3. Production of an abnormal protein. An example is phenylketonuria which is due to production of an inactive form of the enzyme that hydrolyses the amino acid phenylalanine. This leads to delayed milestones in childhood, seizures, learning disabilities and mental retardation as well as reduced or absent pigmentation of skin, hair and eyes. 

4. Defective transport of proteins. Genetic diseases involving abnormalities in protein transport can manifest in patients as hypopigmentation of skin, defects in cell mediated immunity and/or neurological defects. Bardet-Biedl syndrome where the affected person has mental retardation, retinopathy and is of small stature with poorly developed external genitalia, Charcot Marie Tooth disease and Spinocerebellar ataxias where those affected have ataxic gait along with other neurological abnormalities, Hereditary Spastic paraplegia which causes a pure motor paraplegia, are examples of neurological conditions where the genetic defect affects protein transport within cells. Alzheimer’s disease and Type 2 diabetes mellitus may also have defects in the transport of proteins. The transport of amyloid precursor protein by vesicles has been noted to be defective in the early stages of Alzheimer’s disease.  

Reference: Insights into vesicular transport in inherited diseases