Sickle disease

Patients with sickle trait have fewer symptoms than those with sickle disease. 

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

Embury, S.H. The clinical pathophysiology of sickle-cell disease. Annu. Rev. Med. 37 361-376, 1986. 

In the body, proteins are built up by a series of reactions that in general produce a specific sequence of amino adds. Even tiny errors in this sequence may have serious effects. Among the genetic diseases known to be caused by improper sequencing are hemophilia, sickle cell anemia, and albinism. Sickle cell anemia is caused by the substitution of one valine unit for a glutamic add unit in a chain containing 146 monomers. 

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

Influenza vaccine. Influenza vaccine is recommended annually for children age > 6 months with certain risk factors (including but not limited to asthma, cardiac disease, sickle cell disease, HIV, diabetes see MMWR. 2001 50(RR-4) 1-44), and can be administered to all others wishing to obtain immunity. Children aged <12 years should receive vaccine in a dosage appropriate for their age (0.25 mL if age 6-35 months or 0.5 mL if age >3 years). Children aged <8 years who are receiving influenza vaccine for the first time should receive two doses separated by at least 4 weeks. 

Kumpati, J. (1987). Liposome-loaded phenylalanine or tryptophan as sickling inhibitor A possible therapy for sickle cell disease, Biochem. Med. Metabol. Biol., 38, 170-181. 

Figure 1-1. Examples ofthe two-way street connecting biochemistry and medicine. Knowledge ofthe biochemical molecules shown in the top part of the diagram has clarified our understanding ofthe diseases shown in the bottom half—and conversely, analyses ofthe diseases shown below have cast light on many areas of biochemistry. Note that sickle cell anemia is a genetic disease and that both atherosclerosis and diabetes mellitus have genetic components.

Bunn HF Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997 337 762. 

Manning JM et aJ Normal and abnormal protein subunit interactions in hemoglobins.] Biol Chem 1998 273 19359-Mario N, Baudin B, Giboudeau J Qualitative and quantitative analysis of hemoglobin variants by capillary isoelectric focusing. J Chromatogr B Biomed Sci Appl 1998 706 123-Reed W, Vichinsky EP New considerations in the treatment of sickle cell disease. Annu Rev Med 1998 49 46l. 

The detection of restriction fi agment length polymorphisms (RFLPs) facilitates prenatal detection of hereditary disorders such as sickle cell trait, beta-thalassemia, infant phenylketonuria, and Huntington s disease. Detection of RFLPs involves cleavage of double-stranded DNA by restriction endonucleases, which can detect subtle alterations in DNA that affect their recognized sites. Chapter 40 provides further details concerning the use of PCR and restriction enzymes for diagnosis. 

The classic example is sickle cell disease, which is caused by mutation of a single base out of the 3x10 in the genome, a T-to-A DNA substitution, which in... 

Point mutations Protein folding Transcriptional control Frameshiftand nonsense mutations RNA processing Sickle cell disease P-Thalassemia P-Thalassemia P-Thalassemia... 

Sickle cell disease again provides an excellent example of how recombinant DNA technology can be applied to the smdy of human disease. The substitution of T for A in the template strand of DNA in the P-globin gene changes the sequence in the region that corresponds to the sixth codon from... 

If the genetic lesion is understood and a specific probe is available, prenatal diagnosis is possible. DNA from cells collected from as little as 10 mL of amniotic fluid (or by chorionic villus biopsy) can be analyzed by Southern blot transfer. A fetus with the restriction pattern AA in Figure 40-10 does not have sickle cell disease, nor is it a carrier. A fetus with the SS pattern will develop the disease. Probes are now available for this type of analysis of many genetic diseases. 

Rosse WF et al New Views of Sickle Cell Disease Pathophysiology and Treatment. The American Society of Hematology. www.asheducationbook.org... 

Ischemic stroke has numerous causes. Cerebral infarction may result from large artery atherosclerosis, cardiac embolism, small artery lipohyalinosis, cryptogenic embolism, or, more rarely, from other diverse conditions such as arterial dissection, infective endocarditis, and sickle cell disease. Arterial occlusion is the cause of at least 80% of acute cerebral infarctions. " ... 

Keshan disease (selenium deficiency) Sickle cell anaemia... 

Systemic lupus erythematosus, Sjogren s syndrome, multiple myeloma, obstructive uropathy, cirrhosis, and sickle cell disease... 

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