Every cell in our body has thousands of different proteins, each with its own job to do. Some of these proteins have very specialised active jobs, and these are called enzymes.
Medium chain acyl-CoA dehydrogenase (MCAD) is one such enzyme. It is responsible for the breakdown of the fat we absorb in our diet to provide energy for the body. It is the second most important energy provider after the breakdown of glucose, and is therefore crucial for maintaining health. However, when the enzyme is unable to do its job, this can have a drastic effect, leading to a disease called MCAD deficiency.
The symptoms of this deficiency are quite broad, ranging from low blood sugar and seizures to coma and death. The symptoms differ from patient to patient. In general, however, there is a progression of the severity of the symptoms, with an increasing number of episodes of the disease. Early diagnosis is therefore essential to prevent a fatal outcome.
However, due to the rarity of the disease, and the non-specificity of the symptoms, the disease often goes unrecognised in the initial stages. MCAD often affects neonates and young children, and has, therefore, been linked to Sudden Infant Death Syndrome (SIDS), as babies die suddenly with no obvious cause of death. This is not to say that every SIDS case is caused by MCAD deficiency. It is likely, however, that some deaths due to MCAD deficiency go unrecognised, and are therefore mislabelled as SIDS.
Although this disease can be fatal, it is very easily treated, with one response to follow a high carbohydrate, low-fat diet. At the first sign of any illness, the patient takes a high carbohydrate drink (any of the commercially available "high-energy" or "sports" drinks), which is enough to prevent the attack from progressing. The drink provides extra glucose to make energy, so stress on the breakdown of fat is avoided.
Once the deficiency has been successfully diagnosed, the majority of patients avoid further episodes of the disease. It was generally thought that once these severe episodes were avoided, the patient remained relatively normal.
However, recent studies have shown that even patients who avoid further episodes of the deficiency still have a significantly increased risk of developmental disability, chronic illness, mental retardation, decreased muscle development, and a 50 per cent increased chance of developing Attention Deficit Disorder (ADD). These "secondary" symptoms may arise from injury to the brain caused by seizures, or a build up of products from abnormal fat breakdown that is toxic to the brain.
MCAD is a genetic disease, and therefore can be passed down from one generation to the next. As there are thousands of enzymes needed in every cell of the body, each doing its own specific job, the body does not keep a ready supply of each protein on hand.
Instead, the body keeps only a "master copy" of each protein, and these master copies are called genes. When the body needs a specific protein it will read the master copy and use the information to make the needed protein, much like a blueprint is used to construct a house.
All proteins are made up of building blocks called amino acids. These amino acids are joined together in a chain to form a protein. Each protein is unique, differing in how many and in which order these amino acids are placed, and it is this detailed information that is stored in the genes.
However, the protein cannot function as a long chain, it must "fold" up in order to be able to work. This folding happens because different amino acids on the chain are attracted to each other, so they come together, much like joining the pieces of a jigsaw puzzle, and the protein can fold into its 3-D shape. It is in this shape that the protein is now able to do its job.
If there is a mistake, a mutation in the gene used to construct protein, the mistake will be incorporated into the protein and the wrong amino acid will be placed on the protein chain. Depending on which amino acid is substituted, this defect may have a drastic effect on the ability of the protein to fold correctly. As with the jigsaw puzzle, if a piece is put in the wrong place, it affects how the surrounding pieces will join.
British studies estimate that the probability of being genetically predisposed to MCAD is one in every 18,500 people. However the number of patients presenting is significantly less than this, approximately one per two million. This is because patients remain without symptoms if "environmental triggers" are avoided.
These triggers range from fever, infection, fasting sickness, and childhood inoculations, anything that could cause metabolic stress. Under normal conditions of MCAD deficiency, the body can cope with its energy demands, but when there is extra energy required to fight off infection, the body can no longer cope, and can shut down.
Although the number of patients appears very low when compared with other diseases, such as cancer or heart disease, it affects quite a high number compared with other prevalent genetic diseases, which is why MCAD deficiency is considered a "common" genetic disease.
Surprisingly, it is not routinely screened for in newborns. This is despite a disease rate similar to that for phenylketonuria (PKU), another common metabolic disorder which is routinely screened for at birth.
MCAD deficiency meets all the criteria for newborn screening; it is a common inherited disease, can result in a serious disease, may be fatal, yet can be easily averted through simple dietary means. This is especially important, as early detection is crucial to preventing the progression of this disease. This strongly suggests that it is not so much the disease itself, but lack of diagnosis makes the problem worse.
The deficiency is caused by a single mutation within the gene. There is one common mutation, which accounts for 85 per cent of all cases of this disease. It has been shown that this mutation prevents the protein from folding up correctly, which therefore affects its ability to break down fat.
All cases of this mutation detected so far have been found in Caucasians of north-west European extraction. A Danish study has shown that this mutation is more prevalent in north- western European countries especially Ireland, England and Denmark, than those in the south and east, such as Italy. MCAD is non-existent in Japan.
The other 15 per cent of MCAD deficiency cases are caused by a variety of about 30 different rare mutations. These mutations can be so rare that there might only be a single known case in the entire world.
A number of these rare mutations are currently being studied in the department of biochemistry at University College, Dublin. The aim is to determine how exactly these mutations affect the folding, linking this to the severity of the disease.
The Royal Irish Academy/Irish Times biochemistry essay competition is open to third-level students north and south who are asked to write a research article suitable for a newspaper. Her prize includes a bronze statue and a cheque for £800, both sponsored by Yamanouchi (Ireland) Co Ltd.