Broad beta disease

Familial type III hyperlipoproteinemia (broad beta disease, remnant removal disease, familial dysbetalipoproteinemia) Deficiency in remnant clearance by the liver is due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor. Increase in chylomicron and VLDL remnants of density < 1.019 (P-VLDL). Causes hypercholesterolemia, xanthomas, and atherosclerosis. 

Hazzard WR, Porte D Jr., Bierman EL (1972) Abnormal lipid composition of very low density lipoproteins in diagnosis of broad-beta disease (type 3 hyperlipoproteinemia). Metabolism 21 1009-1019... 

Production of LDL from VLDL in the plasma With these modifications, the VLDL is converted in the plasma to LDL. An intermediate-sized particle, the intermediate-density lipoprotein (IDL) or VLDL remnant, is observed during this transition. IDLs can also be taken up by cells through receptor-mediated endocytosis that uses apo E as the ligand. [Note Apolipoprotein E is normally present in three isoforms, E2, E3, and E4. Apo E2 binds poorly to receptors, and patients who are homozygotic for apo E2 are deficient in the clearance of chylomicron remants and IDLs. The individuals have familial type III hyperlipoproteinemia (familial dysbetalipoproteinemia, or broad beta disease), with hypercholesterolemia and premature atherosclerosis. Not yet understood is the fact that the E4 isoform confers increased susceptibility to late-onset Alzheimer disease.]... 

Type 111 (familial dysbetaMpoproteinaemia, remnant removal disease, broad beta disease, apolipoprotein E deficiency)... 

III Broad beta disease Increased (3-VLDL levels Imperfect clearance of lipoprotein remnants... 

Liver disease is a major cause of all kinds of abnormal lipoproteins. In lipoprotein electrophoresis it often causes a boring pattern no alpha-lipoproteins and a very broad beta-band. The latter is due to a host of abnormal or abnormally composed lipoproteins. In summary, we find decreased alpha-lipoproteins, a dissociation of A-I and A-II (a rare instance of the presence of LP-A-II) decreased LP-B, abnormal VLDL, poor in Apo-C, remnants in the LDL-class, and LP-X. 

More broadly, timolol therapy should be considered with caution in patients with any significant sign, symptom, or history for which systemic beta-blockade would be medically imwise.This includes disorders of cardiovascular or respiratory origin (e g., asthma, chronic bronchitis, and emphysema) as well as many other conditions. Spirometric evaluation after institution of timolol therapy may help to identify patients in whom bronchospasm develops after commencement of therapy. In general, however, patients with asthma and other obstructive pulmonary diseases should avoid this drug. Sympathetic stimulation may be essential to support the circulation in individuals with diminished myocardial contractility, and its inhibition by P-adrenoceptor antagonists may precipitate more severe cardiac feilure. 

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