In this situation, the individual would have three copies of part of one chromosome (two normal copies and the portion that exists on the derivative chromosome) and only one copy of part of the other chromosome involved in the derivative chromosome. Robertsonian translocations, for example, account for a very small minority of Down syndrome cases (<5%). The formation of one isochromosome results in partial trisomy of the genes present in the isochromosome and partial monosomy of the genes in the lost arm. Aneugens
Agents capable of causing aneuploidy are called aneugens. Many mutagenic carcinogens are aneugens. X-rays, for example, may cause aneuploidy by fragmenting the chromosome; it may also target the spindle apparatus. Other chemicals such as colchicine can also produce aneuploidy by affecting microtubule polymerization. Exposure of males to lifestyle, environmental and/or occupational hazards may increase the risk of spermatozoa aneuploidy. Tobacco smoke contains chemicals that cause DNA damage. Smoking also can induce aneuploidy. For instance, smoking increases chromosome 13 disomy in spermatozoa by 3-fold, and YY disomy by 2-fold.Occupational exposure to benzene is associated with a 2.8-fold increase of XX disomy and a 2.6-fold increase of YY disomy in spermatozoa.Pesticides are released to the environment in large quantities so that most individuals have some degree of exposure. The insecticides fenvalerate and carbaryl have been reported to increase spermatozoa aneuploidy. Occupational exposure of pesticide factory workers to fenvalerate is associated with increased spermatozoa DNA damage. Exposure to fenvalerate raised sex chromosome disomy 1.9-fold and disomy of chromosome 18 by 2.6-fold.
Insulin autoimmune syndrome (IAS), a rare cause of reversible autoimmune hypoglycemia also known as Hiratas disease, was first described by Hirata in Japan in 1970. Signs and symptoms
Affected patients are usually adults, experiencing multiple episodes of spontaneous hypoglycemia with neuroglycopenic symptoms. Causes
The cause of IAS is not clearly understood. However, interaction of disulfide bond in the insulin molecule with sulfhydryl group drugs such as methimazole, carbimazole, captopril, isoniazid, hydralazine, imipenem, and also with lipoic acid has been suggested. Drug-induced autoimmunization is evidenced by insulin autoantibodies appearing a few weeks after the intake of drug containing the sulfhydryl group. Additionally, IAS has a significant genetic predisposition as its association with specific HLA class has been observed. Pathophysiology
Following a meal, glucose concentration in the bloodstream rises, providing a stimulus for insulin secretion. Autoantibodies bind to these insulin molecules, rendering them unable to exert their effects. The resultant hyperglycemia promotes further insulin release. As glucose concentration eventually falls, insulin secretion also subsides, and the total insulin level decreases. Now insulin molecules spontaneously dissociate from the autoantibodies, giving rise to a raised free insulin level inappropriate for the glucose concentration, causing hypoglycemia. Diagnosis
Usual presenting features are multiple episodes of spontaneous hypoglycemia and appearance of insulin autoantibodies without prior history of administration of exogenous insulin. The insulin level is significantly high, usually up to 100 mIU/L, C-peptide level is markedly elevated, and insulin antibodies are positive. Treatment
The best known treatment is recommending frequent, small meals and to avoid simple sugars.