An Inherited Metabolic Disorder is a genetic (hereditary) disorder caused by a mutation (alteration) in a gene that results in a single enzyme to be completely deficient or not working as it should.
The role of that enzyme is hugely important to the bodies normal metabolic pathways responsible for how the body functions. If an enzyme is missing or not doing an important job, its absence means toxic chemicals may build up, or an essential material may not be produced. For some IMDs it is not fully known what gene defect is the cause and for some they are so rare that little is known about them. However, for many there are some similarities which can be useful in aiding our understanding of the different types of IMDs.
Amino Acid Disorders
Amino acids are the building blocks of proteins. Disorders are caused by defects in the breakdown of amino acids and toxic substances build up in the body. As the body cannot process proteins properly, people with these disorders are unable to eat high protein foods. Illness or infection, incorrect dietary management, or fasting can cause serious health problems and in some cases can be life threatening.
Urea Cycle Disorders
A urea cycle disorder (UCD) is a genetic (hereditary) disorder caused by a mutation (alteration) in a gene that results in one of the six enzymes in the urea cycle in the liver to not work properly. The urea cycle changes waste ammonia, which is potentially toxic (poisonous), to a compound called urea which is then removed from the body in the urine.
In UCDs, one of the enzymes in the cycle does not work properly. Without all the enzymes working as they should, the process can’t be completed and ammonia builds up in the blood, a process called Hyperammonemia. This process can lead to a Hyperammonemic crisis (HAC) which is a highly toxic condition and can cause a range of behavioral problems and other symptoms. If enough ammonia builds up in the blood, it can affect the brain, and may cause irreversible brain damage, coma or death.
UCDs are rare, affecting 2,100 people in Europe. The US incidence is thought to be one UCD patient for every 35,000 births, representing about 113 new patients each year across all age groups. UCD incidence in Europe is expected to be similar.
For more information on Urea Cycle Disorders including emergency guides visit The British Inherited Metabolic Disease Group
For useful guides for you and your family or if you are a professional needing more information please visit the European Inherited Metabolic Disease Group
Mitochondrial Disorders and Peroxisomal Disorders
Mitochondria are often called the “battery” of the cells, they produce most of the energy that is needed by the body and found in nearly every cell in the body. A defect in the function of the mitochondria can cause the cell to fail or cause the cell to die. The mitochondria have its own DNA. Mitochondrial Disease affects virtually all of the organs. It is believed that 1 in 200 babies in the UK are born with genetic changes that can cause mitochondrial disease.
Peroxisomes are small structures within the body’s cells that contain enzymes. These enzymes carry out similar functions as the mitochondria, but the peroxisome’s are also needed to break down very long-chain fatty acids (VLCFA’s) so the body can either use them or get rid of them. If there is a defect in the peroxisome, VLCFA’s build up to unhealthy levels. The incidence of peroxisomal disorders is 1:20,000. The peroxisomal disorders have a variety of symptoms which all vary in severity.
Lysosomal, Sterol and Lipid Disorders
There are over 50 Lysosomal Storage Disorders. (The lysosome is the cell’s recycling centre). Enzyme deficiency causes a build-up of a material called substrate inside the lysosome leading eventually to cell degeneration. A build-up of substrate occurs in various tissues and organs of the body. This causes progressive physical and mental deterioration, and eventually death. As a group, LSD’s have a prevalence of 1 per 7,700* births in some countries. Sterols are a type of lipid, the most well-known being cholesterol. Lipids include fatty acids, steroids, oils, and other related compounds. They are stored naturally in the body’s cells, organs, and tissues. Lysosomes break down the lipids and proteins to provide energy for the body. Lipid storage diseases cannot break down lipids properly so harmful amounts of lipids accumulate.
Fatty Acid Oxidation Disorders and Organic Acid Disorders
The body uses glucose for energy. When the body uses all of the glucose reserves, it breaks down fat to use as energy. However, if you have a fatty acid oxidation disorder, a genetic defect means that your body is unable break down this fat for energy which is essential for when you have gone for long periods without food, especially if you are unwell. This can cause low blood sugar and harmful substances to build up in his blood. In Organic Acid Disorders, the body is unable to properly break down proteins into amino acids. This is caused by a deficiency of a specific enzyme and creates a harmful imbalance of chemicals in the body
This group of disorders encompasses those which are linked to Inherited Metabolic Disorders and also those for where there is little or no other support group available.
Carbohydrate and Glycosylation Disorders
Carbohydrates are a type of sugar. Sugars, both simple and complex, need to be broken down by specific enzymes so the body can use them. In carbohydrate disorders, an enzyme needed to process a certain sugar is missing or defective. This causes the sugar to accumulate which is harmful and leads to the symptoms of these disorders. Glycosylation disorders cause problems in the production of glycoproteins. These are proteins that have carbohydrates attached to them. Symptoms of glycosylation disorders are widely varied, affecting many organs and systems in the body.
Purine and Pyrimidine Disorders, and the Porphyrias
Purines and pyrimidines are components of our DNA. Both have fundamental roles in genetic processes, and ensuring all the chemical reactions in the body take place correctly. Each step requires a specific enzyme. In rare cases if the enzyme is missing, or not working properly, the purine and pyrimidine pathways can be severely affected. Some relatively well known diseases such as gout are linked to purine metabolism. The porphyrias are a group of eight disorders, each of which is caused by a genetic fault. This means that one of the enzymes involved in the production of harm, doesn’t work properly.
The type of porphyria depends on which enzyme is affected. Although haem is made in all cells of the body, the majority is used in either the bone marrow to make haemoglobin or the liver to support metabolism. When the enzyme is deficient, porphyrins accumulate causing harmful effects.
Hormones are produced by the body and are secreted by a number of different glands which make up the endocrine system. They can also be produced by the kidneys, which produce hormones to help control blood pressure and help in the production of red blood cells. The digestive tract produces hormones that control digestion, affect insulin secretion from the pancreas, and manage behaviours. Fat tissue also produces hormones that coordinate metabolism and appetite.
Blood and Immune System Disorders
This group encompasses genetic blood and immune disorders such as various forms of anemia, clotting/coagulation disorders, abnormalities in cell types, bone marrow failure syndromes, antibody deficiencies, autoinflammatory diseases, immune system disorders and immunodeficiency, amongst others.
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal disorders affect the joints, ligaments, muscles, nerves, tendons, and supportive structures. This group may include inflammatory and /or degenerative conditions. Connective tissue supports organs and other parts of the body, this includes fat, bone, and cartilage. These disorders often have symptoms which affect the joints, muscles, and skin, but they can also involve other organs and organ systems. There are a large number of connective tissue disorders, however, genetic ones are quite rare.