Transcript Case Study :Bloom Syndrome

Case Study :Bloom
Syndrome
By: Roslyn A. Espiritu
Bloom Syndrome
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Definition: An autosomal recessive disorder
characterized by telangiectatic ERYTHEMA of
the face, photosensitivity, DWARFISM and other
abnormalities, and a predisposition toward
developing cancer. The Bloom syndrome gene
(BLM) encodes a RecQ-like DNA helicase.
Causes
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Mutations in the BLM gene (located on chromosome 15) cause
Bloom syndrome. This gene provides instructions for the
production of the Bloom (BLM) syndrome protein, which is a
member of the DNA helicase family. The BLM protein helps stabilize
the DNA when cells replicate. Mutations in the BLM gene reduce the
protein's DNA helicase activity, resulting in chromosomal errors
during replication. Consequently, individuals with Bloom syndrome
have a higher frequency of both chromosome breakage and
rearrangement than unaffected individuals.
Some researchers have suggested that individuals with Bloom
syndrome overproduce the superoxide radical anion. These
researchers claim that inefficient removal of peroxide might be the
cause of chromosal damage and rearrangement.
Symptoms
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Circulatory/Dermatologic: Telangiectatic erythema (dilation of blood vessels)
appears as lesions on the skin or as butterfly-shaped patches of reddened skin on
the face and other areas exposed to the sun. The sclera (white, protective, outer
layer of the eyeball) blood vessels may also become dilated. Sun exposure worsens
these symptoms.
Gastrointestinal: Newborns with Bloom syndrome are often disinterested in
feeding. Regurgitation and vomiting is common during infancy. Patients should be
evaluated for gastroesophageal reflux.
Immunodeficiency: Bloom syndrome causes decreased levels of immunoglobulin
A and immunoglobulin M, which leads to recurrent respiratory and gastrointestinal
tract infections.
Neoplasia (tumors): The chromosomal instability of Bloom syndrome patients
causes an elevated cancer risk in affected individuals. Bloom syndrome patients are
150 to 300 times more likely to develop cancer compared to the general population.
About 20% of Bloom syndrome patients develop malignancies. The cancers usually
arise early in life, as individuals may be first diagnosed with cancer when they are
about 25 years old.
Symptoms
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Physical features: Usually the first physical symptom of Bloom syndrome is growth
delay, which has a prenatal onset and persists throughout life. More than 50% of
children with Bloom syndrome are significantly underdeveloped in physical stature
until they are eight years old. Adults with Bloom syndrome have short stature.
Bloom syndrome patients typically have long limbs, disproportionately large hands
and feet and progressive contracture of hands and feet. Upper extremities are long in
proportion to body length. Individuals with Bloom syndrome usually have a highpitched voice, a long narrow face, small lower jaw and prominent nose and ears.
Cheilitis (dry, cracked lips) with crusting or bleeding may also occur.
Pulmonary: Bacterial respiratory tract infection is a common symptom of Bloom
syndrome. If untreated, respiratory tract infections may progress to chronic
bronchiectasis (chronic dilatation of the bronchi). Chronic pulmonary disease is the
second most common cause of death in Bloom's syndrome.
Reproductive: Patients have primary hypogonadism (underactive sex organs).
Women with the disorder usually experience menopause earlier than unaffected
women.
Other: Other symptoms may include learning disabilities, mental retardation and
diabetes.
Diagnosis
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Prenatal diagnosis (at about 15-18 weeks gestation) is possible with
amniocentesis. The amniotic fluid cell culture is evaluated to
determine whether there is a high number of sister chromatid
exchanges. Also, DNA analysis is expected to be available in the
future.
A laboratory test called a chromosome study is used to diagnose
patients with Bloom syndrome. The test, which is performed at the
U.S. National Institutes of Health (NIH) and U.S. Armed Forces
Institute of Pathology laboratories, evaluates chromosome stability,
including sister chromatid exchanges, by looking at blood and skin
cells.
In addition, immunoglobulin levels are evaluated. Individuals with
Bloom syndrome have decreased levels immunoglobulin A and
immunoglobulin M, with or without immunoglobulin G changes
Treatment
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Currently, there is no specific treatment for the underlying cause of
Bloom syndrome. However, avoiding sun exposure and using
sunscreens may help reduce some of the cutaneous symptoms.
Patients should also minimize exposure to known mutagens (agents
that can potentially cause genetic mutations) like X-rays, ultraviolet
light and various chemicals.
Growth hormone therapy has been used unsuccessfully to increase
height in children with Bloom's syndrome. Also, there is some
concern that the use of growth hormone may increase the risk for
cancer later in life.
Bloom syndrome patients should be screened regularly for cancer.
Surgical and/or oncology care may be necessary for the diagnosis
and treatment of malignancies.
Integrative Therapies
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Strong scientific evidence :
Vitamin A : The prescription drug All-Trans-Retinoic Acid (ATRA, Vesanoid®) is a vitamin A derivative that is an
established treatment for acute promyelocytic leukemia and improves median survival in this disease. Treatment
should be under strict medical supervision. Vitamin A supplements should not be used simultaneously with ATRA
due to a risk of increased toxicity. If pregnant or breastfeeding, vitamin A should only be used within the
recommended dietary allowance.
Good scientific evidence :
Probiotics : There is recent evidence that supplementation with Lactobacillus casei may help reduce the
recurrence of colorectal tumors in patients who have previously undergone surgery for colon cancer. Probiotics are
generally regarded as safe for human consumption. Long-term consumption of probiotics is considered safe and
well tolerated.
Psychotherapy : There is good evidence that psychotherapy can enhance cancer patients' quality of life by
reducing emotional distress and aiding in coping with the stresses and challenges of cancer. Therapy may be
supportive-expressive therapy, cognitive therapy or group therapy. Studies conflict on whether therapy improves
self-esteem, death anxiety, self-satisfaction, etc. While some patients seek psychotherapy in hopes of extending
survival, there is no conclusive evidence of effects on medical prognosis.
Selenium : Initial evidence has suggested that selenium supplementation reduces the risk of developing prostate
cancer in men with normal baseline PSA (prostate specific antigen) levels, and low selenium blood levels. This is
the subject of large well-designed studies, including the Nutritional Prevention of Cancer Trial (NPC), and the
ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT), as well as prior population and case-control
studies. There is evidence that low selenium levels are associated with an increased risk of prostate cancer, and
several mechanisms for the beneficial effects of selenium supplementation have been suggested.
Prevention
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Since Bloom syndrome is a genetic
disorder, no preventative measures can be
taken against the disorder. However,
prenatal diagnosis is possible with
amniocentesis. Also, DNA analysis is
expected to be available in the future.
Bibliography
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Gene Tests. www.genetests.org. Accessed
March 16, 2007. Genetics Home Reference.
http://ghr.nlm.nih.gov. Accessed March 16, 2007.
Geneva Foundation for Medical Education and
Research. www.gfmer.ch. Accessed March 16,
2007. Mount Sinai School of Medicine.
www.mssm.edu. Accessed March 16, 2007.
Natural Standard: The Authority on Integrative
Medicine. www.naturalstandard.com.