Abstract
This chapter discusses nine genetic disorders affecting the endocrine and immune systems of the body. These include congenital adrenal hyperplasia, adrenoleukodystrophy, Cockayne syndrome, diastrophic dysplasia, autoimmune polyglandular syndrome, asthma and allergy, severe combined immunodeficiency (SCID), immunodeficiency with hyper-IgM syndromes, and DiGeorge syndrome. The endocrine system made is a complex collection of hormone-producing glands involved in the control of basic body functions such as metabolism, behaviour, growth, and sexual development. The immune system is a complex and highly developed system which protects the body from pathogenic invaders and other foreign molecules or particles like allergens. The body uses three lines of defence against invaders, two of them non-specific and one highly specific. Most immune disorders result from either an excessive immune response or an “autoimmune attack.”
TopChapter Outline
16.1 Overview of Immune and Endocrine Systems
16.2 Congenital Adrenal Hyperplasia
16.3 Adrenoleukodystrophy
16.4 Cockayne Syndrome
16.5 Diastrophic Dysplasia
16.6 Autoimmune Polyglandular Syndrome
16.7 Asthma
16.8 Severe Combined Immunodeficiency
16.9 Immunodeficiency with Hyper-IgM
16.10 DiGeorge Syndrome
Chapter Summary
TopLearning Outcomes
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Identify each genetic disorder affecting each system
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Outline the symptoms of each disorder
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Explain the genetic basis of each disorder
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Summarize the therapies currently available to treat each disorder
Top16.1 Overview Of Endocrine And Immune Systems
The endocrine system made is a complex collection of hormone-producing glands involved in the control of basic body functions such as metabolism, behaviour, growth, and sexual development (Figure 1). These endocrine glands are the pituitary, pineal, thyroid and parathyroid, thymus, adrenals, pancreas, and the gonads (ovaries and testes). Hormones are protein secretions made in glands and used in the body as chemical signals and secreted directly into the bloodstream for transport. Blood carries them to distant tissues and organs where they can bind to specific cell sites embedded in the cell membrane made of integral proteins called receptors. Once they bind, hormones can trigger various responses in the tissues containing the receptors. Steroid hormone signals like those coming from oestradiol or aldosterone freely diffuse through the plasma membrane of cells (no receptors at the surface) to bind molecules in the cell cytoplasm.
Figure 1. The major human endocrine organs
Protein hormones like insulin, cortisol, epinephrine, glucagon, etc. use a variety of mechanisms once they bind a receptor at the cell surface initiating a signal transduction process as discussed in Chapter 3 (section 3.3). Specific protein receptors embedded in the cell membrane bind the signals, enabling conformational changes inside channel or transport proteins which transport the signal to the cytoplasm. There are three types of protein receptors for non-steroidal signals: G-protein coupled receptors (GPCR), receptor tyrosine-kinases & ion channel proteins. Non-steroid signals activate other molecular or ionic mediators in the cytoplasm which include GPCRs, G-proteins, effector proteins, and receptor proteins for 2nd messengers (protein kinases A, G, C and calmodulin kinase). Transduction involves several protein molecules in a phosphorylation cascade and other multiple mediators (broadly called second messengers). Such second messengers are ions (like Ca2+), lipid metabolism products (like diacylglycerol [DAG], inositol triphosphate [IP3] and phosphatidyl-inositol-biphosphate [PIP2]), nucleotides (like cyclic AMP or cyclic GMP), and a variety of protein mediators that relay, adapt, transduce, anchor, integrate, modulate or amplifier signals (Chapter 3, section 3.3).
The immune system is a complex and highly developed system which protects the body from pathogenic invaders and other foreign molecules or particles like allergens. Pathogens are viruses, bacteria, fungi, protozoans, and parasitic worms that cause disease or disease symptoms. Individuals with severely defective immune systems can die from infection when pathogens overwhelm the body’s ability to seek and attack invaders. The body has three lines of defence against invaders, two of them non-specific, and one highly specific.
Key Terms in this Chapter
Polyendocrinopathy: A condition when the body develops multiple autoimmune disorders in the endocrine system.
Atelosteogenesis: One of many conditions that affect the development of bone and cartilage of infants that have varying degrees of severity.
Addison’s Disease: A disorder in which the adrenal gland insufficiently produces cortisol and aldosterone.
Axonopathy: Degradation of the axons of peripheral nerves.
Hypogammaglobulinemia: An immune disorder in which there is a reduction in serum gamma globulins.
Scoliosis: A condition that causes an abnormal curve to the spine.
Achondrogenesis: A group of conditions that affect the development of bone and cartilage.
Dysplasia: A phase where cells are not cancerous but look abnormal under a microscope.
Alopecia: Hair loss in round patches.
Allogeneic Stem-Cell Transplantation: A treatment involving stem cell transfer from a healthy donor to the patient after chemotherapy or radiation.
Demyelination: Damage to the protective myelin sheath covering the nerve fibres.
Ectodermal Dysplasia: A group of genetic disorders involving the abnormal development of two or more ectodermal structures: skin, sweat glands, nails, teeth, hair, and mucous membranes.
Lymphoid Hyperplasia: An increase in lymphocytes resulting in the enlargement of lymphoid tissue.
Hypoparathyroidism: A condition in which there is a deficiency in the production of parathyroid hormone.
Hyperplasia: Enlargement of an organ caused by an increased number of cells.
Lenti-D Gene Therapy: A form of gene therapy that utilizes the lentivirus as the cloning vehicle.