Genetic disorders hepatic

Ribozymes have been applied as anti-viral agents, for the treatment of cancer and genetic disorders, and as tools for pathway elucidation and target validation. Initial uses of ribozymes focused on anti-viral, primarily for the treatment of HIV (Rossi, 1999). Viruses that go through a genomic RNA intermediate in their replication cycle, such as HIV, hepatitis B virus and hepatitis C vims are attractive targets because a single... 

Interferon, a small protein containing fewer than two hundred amino acids, is an interesting example of a biologically active polypeptide. There are three classes of interferon, labeled by the first three letters of the Greek alphabet. Interferon-a is used to treat leukemia, hepatitis B and C, and Kaposi s sarcoma. Interferon-/3 finds use as a treatment for multiple sclerosis and interferon-y has applications in treating a rare genetic disorder called granulomatous disease. 

Schmitz G, Becker A, Aslanidis C (1996) ACAT/CEH and ACEH/LAL two key enzymes in hepatic cellular cholesterol homeostasis and their involvement in genetic disorders. Z Gastroenterol 34(Suppl 3) 68-72... 

Biochemical basis of disorder Because of a genetic disorder, the hepatic aldolase B enzyme is defective, and functions normally in glycolysis but not in fructose metabolism. Glucose production is inhibited by elevated fructose 1-phosphate. When fructose is ingested, severe hypoglycemia results. 

Without the enzyme microsomal triglyceride transfer protein (MTP), hepatic triglycerides cannot be transferred to apoB-100. Patients with dysfunctional MTP fail to make any of the apoB-containing lipoproteins (VLDL, IDL, or LDL). MTP also plays a key role in the synthesis of chylomicrons in the intestine, and mutations of MTP that result in the inability of triglycerides to he transferred to either apoB-100 in the liver or apoB-48 in the intestine prevent VLDL and chylomicron production and cause the genetic disorder abetalipoproteinemia. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Definition of porphyrias, their modes of genetic inheritance, and their treatment Porphyrias are caused by inherited (or occasionally acquired) defects in heme synthesis, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. Porphyrias are classified as erythropoietic or hepatic, depending where the enzyme deficiency occurs. With the exception of congenital erythropoietic porphyria, which is a genetically recessive disease, all the porphyrias are inherited as autosomal dominant disorders. All porphyrias result in a decreased synthesis of heme and, therefore, ALA synthase is dere-pressed. The severity of symptoms of the porphyrias can be diminished by intravenous injections of hemin. Because some porphyrias result in photosensitivity, avoidance of sunlight is helpful. 

A number of other factors, including genetic or biological factors, that are possibly associated with the development of psychiatric disorders, have been explored. In a retrospective study of 110 patients with chronic hepatitis C, those with the apolipoprotein E e4 allele, the inheritance of which may be associated with several neuropsychiatric outcomes, were more likely than those without this allele to have psychiatric referrals and neuropsychiatric symptoms, in particular irritability, anger, anxiety, or other mood symptoms, during interferon alfa treatment... 

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