metabolic disorder

(medicine) Any disorder that involves an alteration in the normal metabolism of carbohydrates, lipids, proteins, water, and nucleic acids; evidenced by various syndromes and diseases.

Disorders of metabolism principally involve an imbalance in nucleic acids, proteins, lipids, or carbohydrates. They are usually associated with either a deficiency or excess resulting in an imbalance in a particular metabolic pathway. All metabolic disorders have a genetic background, and some of them are expressed as specific genetic diseases. Other factors affecting metabolism include internal control mechanisms that are superimposed on the genetic background. One of the most important mechanisms is the hormonal control system, which consists of the endocrine, paracrine, and autocrine systems. The second control system that has a significant effect on metabolism is the neural control system. The third control system is the immune control system, which relates to both the endocrine and neural systems. Genetic background, environmental factors, and the three major control mechanisms, in conjunction with age and sex, bring about profound changes in metabolism, which ultimately result in structural and functional alterations. See also Immunology; Nervous system (vertebrate).

Nucleic acids

Abnormalities of nucleic acid metabolism are associated with several diseases, including gout and lupus erythematosus. All genetic disease implies a defect in nucleic acids, and although some genetic diseases are classified as protein abnormalities there is always an inherent defect in the nucleotide. This is either a deficiency, an excess, or a mutation that results in an abnormal protein being formed. Similarly, although lipid storage disease results in an abnormal metabolism of lipids, it is the result of a deficiency of a particular enzyme, which also means a defect in the particular nucleic acid code. In some carbohydrate genetic storage diseases, there is a deficiency of a particular enzyme, which again results from a nucleotide defect. Certain congenital defects that result in malformations of organ systems are the result of either germ cell or somatic cell deficiencies involving differentiation genes composed of nucleic acid.

The genetic disease severe combined immunodeficiency syndrome (SCIDS) results in a deficiency of B lymphocytes, which produce antibody, and T lymphocytes, which are responsible for graft and tumor rejection as a result of their cytotoxic effect. This abnormality is associated with a deficiency of the enzyme adenosine deaminase. See also Arthritis; Connective tissue; Disease; Gout; Human genetics; Nucleic acid.

Proteins

The diseases associated with protein abnormalities include those associated with increased production of proteins, decreased production of proteins, production of abnormal proteins, and excretion of unusual amounts of amino acids.

Often called macroglobulinemia, hyperproteinemia results in an increase in beta or gamma globulins, but possibly with less total protein. Hyperglobulinemia diseases include multiple myeloma, kala-azar, Hodgkin's disease, lymphogranuloma inguinale, sarcoidosis, cirrhosis, and amyloid disease. They usually involve stem cell lines of the bone marrow macrophages or B cells. See also Cirrhosis; Hodgkin's disease.

A decrease in the amount of protein (hypoproteinemia) can result from a lack of amino acids for protein synthesis, a metabolic block, or other interference with normal protein synthesis. Increased excretion of protein, particularly in chronic renal disease with a loss of albumin in the urine (albuminuria), is another common cause of hypoproteinemia. Kwashiorkor is the best example of hypoproteinemia resulting from dietary deficiency. In hypogammaglobulinemia and agammaglobulinemia, which may also be classified under hypoproteinemia, the total serum albumin and globulin are not markedly depressed, but the gamma globulins may fall from a normal of 15–20% of total protein to 0.4%.

Many diseases are characterized by abnormal proteins, including multiple myeloma, the hemoglobinopathies, and the various amyloid disturbances. Multiple myeloma, a neoplastic growth of plasma cells, particularly in the bone marrow and lymph nodes, is representative of a disease in which an abnormal protein is produced. Another large group of abnormal proteins includes the hemoglobinopathies. Hemoglobin functions in the transport of oxygen in the blood. Scores of different hemoglobins have been identified, but sickle cell in the United States and thalassemia (Mediterranean anemia) in Europe are two of the most common hemoglobin abnormalities. A third type of abnormal protein is found in amyloid disease, of which there are many variations. See also Amyloidosis; Hemoglobin; Sickle cell disease.

A fourth group with abnormal protein metabolism is associated with a change in particular amino acids resulting either from an overflow mechanism, where the concentration of amino acids in the serum surpasses the renal threshold of the glomerular membrane, or from defective absorption of amino acids in renal tubules. Tyrosine appears to be one of the most critical amino acids, and its metabolism is related to four key diseases including phenylketonuria, hypothyroidism, albinism, and alkaptonuria. The liver plays a major role in the deamination of amino acids. Advanced hepatitis and cirrhosis may lead to increased levels of amino acids in the blood and excretion in the urine. Other diseases with amino aciduria that are believed to be the result of defective kidney function include cystinuria (the failure to reabsorb cystine, lysine, arginine, and ornithine), Wilson's disease (a degeneration involving copper metabolism in the liver and brain), Fanconi's syndrome, galactosemia, scurvy, rickets, and lead, cresol, or benzene poisoning. See also Kidney disorders; Liver disorders; Phenylketonuria; Protein metabolism; Sickle cell disease.

Lipids

Although lipid stores remain a secondary energy reserve in starvation, the breakdown of lipids associated with diabetes and starvation results in the production of ketone bodies in the urine with general acidosis (ketosis) in the serum. Of concern to many people is an increase in lipids associated with obesity. See also Obesity.

Hyperlipemia, an excess of lipid in the blood, is often secondary to uncontrollable diabetes, hypothyroidism, biliary cirrhosis, and lipoid nephrosis. Excess proliferation of fat cells is known as a lipoma, which occasionally becomes malignant, producing a liposarcoma. See also Arteriosclerosis.

In a large group of genetic lipid storage diseases, lipid accumulates because of a disturbance in lipid metabolism that is independent of external stimuli. These genetic diseases are inherent nucleic acid defects that result in abnormal enzymatic proteins, which then result in abnormal lipid metabolism. In these diseases, a large accumulation of lipid appears in many cells, but particularly the reticuloendothelial cells of the lymph nodes, liver, spleen, and bone marrow. Abnormal lipid storage occurs in Niemann-Pick, Gaucher's, and Tay-Sachs diseases.

The heterozygous form of the genetic disease familial hypercholesteremia results in cholesterol levels two to four times normal, and is characterized by arteriosclerotic lesions of the coronary vessels that cause myocardial infarct and death in the 35–50-year age range. In the homozygous condition, with cholesterol levels eight to ten times normal, death occurs usually before the age of 15. The defect resides in the receptor for low-density lipoprotein (LDL). See also Cholesterol; Heart disorders; Lipid metabolism.

Carbohydrates

Abnormal carbohydrate diseases include the genetic diseases that represent a deficiency in nucleotide and eventually protein enzymatic activity. Of the six common carbohydrate storage diseases, two examples are von Gierke's disease, marked by glycogen storage in the heart, and Pompes' disease, in which the carbohydrate is stored in the liver. Variants of carbohydrate disease involve storage of mucopolysaccharides, as in Hurler's disease, and storage of galactose, as in galactosemia.

The most important disease associated with carbohydrate metabolism is diabetes mellitus. See also Carbohydrate metabolism; Diabetes; Metabolism.

The noun has one meaning:

Meaning #1: a disorder or defect of metabolism