Metabolism acquired diseases

Other chronic disorders cause osteomalacia. " " Phosphate depletion from low dietary intake, phosphate-binding antacids, and oncogenic osteomalacia (potentially phosphaturic effect) can cause osteomalacia. Hypophosphatasia is an inborn error of metabolism in which deficient activity of alkaline phosphatase causes impaired mineralization of bone matrix. Acidosis from renal dysfunction, distal renal tubular acidosis, hypergammaglobulinemic states (e.g., multiple myeloma), and drugs (e.g., chemotherapy) compromises bone mineralization. Renal tubular disorders secondary to Fanconi s syndrome, hereditary diseases (e.g., Wilson s disease, a defect in copper metabolism), acquired disease (e.g., myeloma), and toxins (e.g., lead) cause osteomalacia to varying degrees. Chronic wastage of phosphorus and/or calcium limits mineralization, which may be further compromised by acidosis and secondary hyperparathyroidism. 

FIGURE 2 Interrelationship of metabolites in genetic and acquired disease states and their use as biomarkers for amino acid metabolism. Ratios of two metabolite concentrations (molar ratios) improve specificity for detection and characterization of disease. 

Rude RK, Oldham SB. Disorders of magnesium metabolism. In Cohen RD, Lewis B, Alberti KGMM, Denman AM, eds. The metabolic and molecular basis of acquired disease, Vol. 1. London Bailliere TindaU, 1990 1124-48. 

Fig. 49.14. Synthesis and degradation of proteoglycans by chondrocytes. From Cohen RD, et al. The Metabolic Basis of Acquired Disease, vol 2. London Bailliere Tindall, 1990 1859.

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis, usually monoarticular, and is associated with abnormal levels of uric acid in the body, particularly the presence of monosodium urate crystals in synovial fluid. Primary gout is a hereditary disease in which hyperuricemia is caused by an error in uric acid metabolism—either overproduction or an inability to excrete uric acid. Secondary gout refers to those cases in which hyperuricemia is caused by an acquired disease or disorder, such as chronic renal disease, lead poisoning, or myeloproliferative disorders. Gout generally occurs in... 

Primary myopathies fall into a number of discrete groups the inherited diseases of muscle, the metabolic myopathies, the neurogenic disorders, and the acquired disorders of muscle. 

Inspite of all the qualified successes of synthetic drug research achieved in the last four decades to combat infectious diseases of the more than 80,000 different ailments, unfortunately only about one third can be treated with drugs, most of them only symptomatically. The discovery of better, effective and safer drugs is needed to fight the causes of dreadful diseases like cancer, acquired-immuno-deficiency-syndrome (AIDS), arthritis, cardio-vascular diseases, disorders of the central nervous system (CNS), such as Alzheimer s disease and other vital infectious and metabolic diseases like rheumatoid arthritis. 

Analysis of BAs in urine, serum, bile and stool is crucial for the diagnosis of inborn errors of BA metabolism. It is also helpful for understanding their pathophysiological role in acquired hepatic diseases and for monitoring the effects of therapy on metabolism. Several different inborn defects affecting BA synthetic pathway, have been described over last 20 years [7]. 

Inborn metabolic diseases that interfere with heme biosynthesis are called porphyrias. Porphyrias have a variety of symptoms. A deficiency in the enzyme responsible for the condensation of porphobilinogen to the 4-membered ring system leads to a condition called acute intermittent porphyria, which is characterized by occasional episodes of abdominal pain and psychiatric symptoms. Defects in the later enzymes of the pathway lead to an excess accumulation of the uroporphobilinogens in the tissues, where they cause a variety of symptoms, including hairy skin, skeletal abnormalities, light sensitivity, and red urine. Individuals with this disease are still anemic—a condition that can be alleviated somewhat by the heme acquired from drinking blood. This combination of traits sounds like the werewolf and vampire legends of Europe, which may have their base in this rare biochemical disease. 

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