Inherited errors of metabolism are a group of disorders caused by different genetic mutations, which result in the production of incorrect proteins. This alters the physiological functioning of the cell and may result in:
Accumulation of a non-metabolized substrate;
the production of substances through the metabolizing of this substrate by alternative pathways or;
phenotypes resulting from reduced or non-production of the final product.
Pathophysiological effects of an accumulation of non-metabolized substrates depend on the amount of substances accumulated, as well as the level of its toxicity.
These disorders are also known as hereditary defects of metabolism or congenital errors of metabolism and the concept of inborn errors of metabolism was established at the beginning of the 20th century by Garrod (describing 4 known disorders). At present there are more than 700 known disorders / conditions. Knowledge of these disorders has increased progressively since earlier years (Stanbury et al, 1983 & Scriver et al, 1995).
In recent years, many inherited metabolic disorders could only be diagnosed according to syndromic characteristics or histopathology, but now it can be diagnosed biochemically. Enzymatic errors can be identified, as well as the metabolic toxins produced or the lack of metabolites posterior to the enzymatic defect. Many inborn errors of metabolism (IEM) are related to the metabolism of the primary nutrient and their derived products. The human body is extremely sensitive to alterations in the availability of basic nutrients during the period of rapid growth during early childhood. One or more vital organs (brain, liver, kidney, heart, etc) can often be affected by undesirable results of metabolic alterations and therefore nutritional therapy is fundamental for the treatment of this type of disorder - to ensure the adequate growth of the child while preventing the metabolic imbalances common to these diseases.
Although each individual inborn error of metabolism has a low incidence rate, the combined incidence for this group of diseases is 1 out of 500 live newborns. The prognosis of IEM has clearly improved in recent years due to the possibility of early diagnosis and the availability of specific dietary products for each disease.
Inherited errors of metabolism were always associated with a severely sick baby, presenting with acidosis & hyperammonemia and if the baby does not die, mental retardation is usually the prognosis. Although abovementioned clinical description is true for many inborn errors of metabolism, we recognise now that several chronic diseases may be caused by milder types of inborn errors of metabolism. Clinical symptoms in adults or children listed below are easily detectable symptoms and most often the result of a metabolic defect:
ADHD, Autism, Abnormal behavior
Sudden Infant Death Syndrome
Chronic fatigue syndrome
Muscle aches and weakness
Abnormal eating habits or loss of appetite
Hypo- and hypercholesterolemia
………………..and many more.
At present there are almost 700 metabolic diseases known, but since there are almost 3500 genes coded for enzymes, we can expect many more metabolic diseases to be discovered in the future. It is almost impossible to remember the clinical indications for all the metabolic diseases and since the clinical symptoms may vary, depending on the mutation and detoxification capacity of the person, a computer assisted approach is recommended. Such a program is currently under development and will soon be available. After a clinical selection has been obtained, simple screening tests can be done for further confirmation of the suspicion. Finally the diagnosis must be confirmed by a Laboratory for Inborn Errors of Metabolism.
Many of the metabolic diseases are treatable. Treatment includes special diets, supplementations, stimulation of the detoxification processes, enzyme inhibitors and the establishment of a certain life style.
Potchefstroom Laboratory for Inborn Errors of Metabolism