Causes and Symptoms (Magill’s Medical Guide, Sixth Edition)
Metabolic disorders of all types are usually inherited from one or both parents who carry a defective gene; the gene is one that codes for an enzyme responsible for a part of the metabolic pathway (either anabolic or catabolic). Much like an assembly line that takes raw material and produces a final product through multiple steps, the metabolism of proteins, lipids, and carbohydrates in the human body requires multiple steps, each with its own enzyme. In some cases, there are multiple pathways to metabolize a particular starting product. In this case, lack of one enzyme may not have a dramatic effect. Other pathways are exclusive, however, and any disruption of an enzyme will lead to disease. In addition to loss of a particular product, some enzyme defects lead to the accumulation of precursor molecules that may be toxic or may interfere with normal function of the cell.
When the deoxyribonucleic acid (DNA) coding for a particular gene is altered, one of three outcomes may be seen: no change (silent mutation), partial loss of ability of the enzyme to do its job (mild disease), or complete loss of enzyme function (mild to severe disease). Diseases in the human are not known for all enzymes that could potentially be lost; this is most likely because disruption of an enzyme that is absolutely necessary in early development of the fetus will lead to early (and undetected) loss of the fetus.
Disorders of metabolism may...
(The entire section is 1568 words.)
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Treatment and Therapy (Magill’s Medical Guide, Sixth Edition)
The most important diagnostic tool available for metabolic disorders is routine neonatal genetic screening. In 2005, a report by the American College of Medical Genetics recommended a core panel of twenty-eight metabolic disorders that should be screened for in all newborn children. This list includes disorders of protein metabolism, carbohydrate metabolism, and lipid metabolism, as well as a few multisystem disorders. Such screening does not prevent disorders but does allow early detection and therefore early intervention with diet, drugs, and other regimens that allow extended life spans for those afflicted.
Once detected, treatment of metabolic disorders is quite varied and is related to the underlying cause of the disorder. For protein/amino acid disorders, dietary restrictions are a key element in treatment. For instance, in PKU, phenylalanine intake must be restricted starting in the first few weeks of life. This means elimination of most forms of natural protein and substitution with phenylalanine-free foods. Patients with homocysteinuria often improve with vitamin B6 (pyridoxine) or vitamin B12 (cobalamin). In maple syrup urine disease, restricting the dietary intake of the three branched-chain amino acids to the minimal amount required for growth and development allows for the best improvement. Vitamin B1 (thiamine) is helpful in those with mild disease; dialysis is used in those with severe disease. Gene...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
Metabolic disorders have existed since the earliest humans roamed the earth, but it was not until the early twentieth century that the mechanism for these disorders was recognized. The term “inborn error of metabolism” was coined by Archibold Garrod, a British physician who published a classic text on the subject in 1923, following a study of children with alkaptonuria. This was the first such treatise to explain how symptoms often seen in sickly children could be explained on the basis of enzyme defects. Many of these diseases, such as diabetes, had been well established and named years before but not yet understood in terms of their biochemistry. The genetic basis for these disorders was not determined until much later—the 1970’s and beyond.
Another early pioneer in this field was the German pediatrician Albert Niemann, who in 1914 described in detail a child with nervous system impairment. This condition later became known as Niemann-Pick disease, when Luddwick Pick took tissue samples from several such children after their deaths and provided chemical evidence of a distinct lipid storage problem.
The discovery of insulin in the 1920’s provided the first opportunity to treat a metabolic disease in a standardized way, as insulin could be extracted and purified in a controlled laboratory setting. The availability of insulin has saved millions of lives since its discovery.
The hope for the...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Gilbert, Hiram F. Basic Concepts in Biochemistry. 2d ed. New York: McGraw-Hill, 2000. Although written as a review for medical students, its simple, no-nonsense approach to metabolism makes it a useful tool for anyone seeking an introduction to human metabolic systems.
Machalek, Alisa Zapp. The Structures of Life. Bethesda, Md.: Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of General Medical Sciences, 2000. General introduction to proteins and how errors in manufacturing them can create problems in the body. Also discusses development of new drugs and other research. Also available at http://publications.nigms.nih.gov/structlife.
Nussbaum, Robert L., Roderick R. McInnes, and Willard F. Huntington. Thompson and Thompson Genetics in Medicine. 7th ed. Philadelphia: Saunders/Elsevier, 2006. An excellent text meant primarily for medical students but readable by anyone with a background in basic biology, it describes many of the important metabolic diseases of the human and their basis in genetic defects.
Scriver, Charles R., et al., eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill, 2001. Probably the most important text in its field, this is an exhaustive look at metabolic diseases, their causes, and their treatment.
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Metabolic Disorders (Encyclopedia of Science)
How are your enzymes working today? Enzymes are chemical compounds that increase the rate at which reactions take place in a living organism. Without enzymes, most chemical changes in an organism would proceed so slowly that the organism could not survive. As an example, all of the metabolic reactions that take place in the body are made possible by the presence of specific enzymes. As a group these chemical reactions are referred to as metabolism.
So what happens if an enzyme is missing from the body or not functioning as it should? In such cases, a metabolic disorder may develop.
A metabolic disorder is a medical condition that develops when some metabolic reaction essential for normal growth and development does not occur.
The disorder known as phenylketonuria (PKU) is an example. PKU is caused by the lack of an enzyme known as phenylalanine hydroxylase. This enzyme is responsible for converting the amino acid phenylalanine to a second amino acid, tyrosine. Tyrosine is involved in the production of the pigment melanin in the skin. Individuals with...
(The entire section is 392 words.)