Genetic counseling for Gaucher disorder patients in Ashkenazi Jewish population call for a comprehensive strategy that entails an accurate diagnosis at both molecular and enzymatic levels and a thorough evaluation of the disorder severity (Rosenbloom and Weinreb, 2013). These plans can prove challenging given the phenotypic heterogeneity faced in this disease. Counseling, therefore, ought to address the pertinent concerns of the patient, which may associate to the assessment of the counselee or the reproductive choices to the couple threatened. Essentially, this counseling offers information and support to those individuals who have or are at risk of developing a genetic disease; Gaucher disorder (Rosenbloom and Weinreb, 2013). As such, this paper focuses on the genetic counseling for Gaucher disorder in Ashkenazi Jewish population based on the most recent data and experience.
Background Information on Gaucher Disease
Genetic diseases, more especially Gaucher Disease was first recognized and described in 1882 by P.C.E Gaucher. Aghion contended that patients with Gaucher condition accumulated a sphingoglycolipid known as glucocerebroside (Mehta, 2006). Since Gaucher is a genetic disorder, it is characterized by a deposition of the glucocerebroside among the cells in the macrophage-monocyte system. It is a result of enzyme glucocerebrosidase deficiency. Although different ethnic groups can suffer from Gaucher disorder, Ashkenazi Jews are at higher risk of developing this disorder due to their specific gene mutation. According to scientists, the founder effect of Gaucher disease occurred in the past hundred years when different gene mutations happened some Ashkenazi Jews. While the carriers of these newly mutated genes were not affected by the disorder, their respective descendants were at a higher risk of developing genetic disorders as a result of inheriting the altered genes (Mehta, 2006). As such, in the Jewish history, different mutated genes responsible for different genetic disorders including that liable for Gaucher disorder have been passed on from one generation to another.
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Causes of Gaucher Disease
Gaucher disease is caused by GBA gene mutations. It is the GBA gene that gives instructions on the making of an enzyme beta-glucocerebrosidase. This enzyme is responsible for the breakdown of glucocerebroside into glucose. It also breaks down the simple fat molecules. As such, the mutation of the GBA gene to a great extent hinders the activity of beta-glucocerebrosidase. With a limited content of this enzyme, glucocerebroside and other related components can, therefore, accumulate and build up to toxic levels within the cells. The outcome is the damaging of body tissues and organs as there is an abnormal accumulation and building up of this compound, therefore, causing the features of Gaucher disorder.
Description of Gaucher Disease
Gaucher disease is an inherited disorder that affects different body tissues and organs. The symptoms of this disorder vary widely among patients. According to researchers, there are various types of Gaucher disorder that are categorized by their characteristic features.
Type 1 Gaucher Disease
This is the most common Gaucher disorder. It is also known as neuronopathic Gaucher disorder (Beutler, 2006). This is because it usually affects the spinal cord and the brain. The features of type 1 Gaucher ranges from mild to severe. For instance, symptoms may include enlargement of the spleen and the liver, low red blood cell count, a decrease in thrombocytopenia, lung disease among others. These signs and symptoms may appear anytime from childhood to adulthood.
Type 2 and 3 Gaucher Disease
These types are also called neuronopathic type of disease because they affect the central nervous system. These types are also characterized by abnormal eye movements, brain damage, and seizures. Type 2 Gaucher disorder can cause a severe medical problem that starts off at infancy (Rosenbloom and Weinreb, 2013). On the other hand, type 3 disorder affects the entire nervous system although it worsens at a slower rate as compared to type 2.
Perinatal Lethal Form Gaucher Disorder
This is the most severe type and it causes life-threatening complications that begin before birth. Signs and symptoms include the swelling occasioned by fluids accumulating before birth, scaly skin, hepatosplenomegaly, severe neurological problems and unique facial features (Rosenbloom and Weinreb, 2013). Most newborns with this condition survive for only a few days after birth.
How Gaucher Disorder is Inherited
Among the Ashkenazi Jews, for one to develop Gaucher disease, he or she must inherit two mutations of the Gaucher Disease. In every human being, genes are paired, and from each pair, a gene is given to the offspring, one from the mother and the other from the father to make a pair (Beutler, 2006). Therefore, for a recessive inheritance of Gaucher disorder to happen, both genes inherited to form a pair must be abnormal.
Frequency of Occurrence
According to studies, Gaucher disorder occurs in approximately 1 in every 50,000 in the general population (Rosenbloom and Weinreb, 2013). The type 1 condition is the most prevalent and it occurs more frequently in the Ashkenazi Jewish population as compared to those from other cultural backgrounds. Approximately, 1 in every 500 individuals of Ashkenazi origin develops Gaucher type 1 condition. However, the other types are not so common in people of Ashkenazi origin.
Genetic Testing for Gaucher Disease
Genetic testing refers to the process of analyzing the human DNA, RNA, proteins, and chromosomes in order to detect the hereditary disorder that is associated with mutations, genotypes, karyotypes among others for clinical purposes. Purposes may include, identifying carries, forecasting risks of the disorder as well as developing both prenatal and clinical diagnosis.
Under genetic testing for Gaucher disease, physicians often use saliva or blood samples. By testing the DNA, the physician is able to identify the patient’s precise gene mutations. One gene mutation indicates that one is a carrier. By being a carrier, it means that one does not exhibit Gaucher disorder symptoms, however, he or she can pass Gaucher gene to offsprings. According to research, more than 400 gene mutations cause Gaucher disorder. Nevertheless, only 4 of these mutations are responsible for about 95% of Gaucher cases in the Ashkenazi Jewish population and nearly 50 % of the cases in universal population (Kornreich et al. 2004). Genetic testing for Gaucher in Ashkenazi Jewish population is done under the categories of predictive, reproductive and diagnostic.
Predictive Genetic Testing for Gaucher Disease
This kind of genetic testing detects gene deviations that enhance an individual’s risk of developing Gaucher disorder before the individual starts to exhibit signs of the disorder. A diagnostic test of an affected individual often gives results that can be significant in recommending a predictive genetic test for family members and relatives (Rosenbloom and Weinreb, 2013). For instance, if a mother is found to have a GBA variant, her relatives may be offered a chance to be tested to find out whether they too carry the variant gene. Predictive genetic testing is important for population screening. For instance, screening of newborns in the Ashkenazi population to determine the evidence of Gaucher disease.
Reproductive Genetic Testing for Gaucher Disease
This kind of genetic testing provides an opportunity to determine those individuals who are at high risk of giving birth to a child with Gaucher disease (Kornreich et al. 2004). Carrier genetic testing can be used to identify these people in a population. Basically, carrier testing identifies those individuals with one variant copy of a gene and a normal one that is related to Gaucher disorder inherited as an autosomal recessive characteristic. Typically, carriers have no symptoms of Gaucher but have the ability to transmit a variant gene to their offspring. Prenatal genetic testing can be used to determine abnormalities in the genes of a fetus whereas a pre-implantation genetic testing can be used in reducing the probability of giving birth to a child with Gaucher disorder in a population.
Diagnostic Genetic Testing
Diagnostic genetic testing for Gaucher disorder is mainly done to identify or otherwise rule out Gaucher condition in an individual. Normally, diagnostic genetic testing is done to confirm the disorder once the basic physical signs and symptoms of Gaucher disorder are evident (Kornreich et al. 2004). The outcome of a diagnostic test can significantly inform the patient's as well as physician's options in managing this disorder.
Ethical Implications
Genetic testing has a wide range of legal, individual and societal implications that necessitates considerations in determining the most appropriate testing procedure to be done in a population. These implications are associated to the general shared genetic risk among relatives, use of genetic testing in reproductive decision making as well as the potential genetic information to cause discrimination and stigma among individuals and the population as a whole (Kornreich et al. 2004). Moreover, the quick development of genomic technology and other unraveled uncertainties on the health implications of genetic testing has triggered significant ethical considerations related to clinical data sharing, healthcare disparity among other result reporting from the genome-scale analysis.
Discussion
The genetic testing and counseling are often gathered and assessed through research. As such, the quality and quantity of the data information tend to vary. Therefore, this brings some level of confidence about the outcome of the findings and conclusions. Moreover, the various public, as well as private entities conducting confirmation reviews, often differ in approaches and strategies for evaluating the available data regarding the utility and validity of genetic tests for Gaucher disorder (Kornreich et al. 2004).
Evidence founded on genetic testing of Gaucher disease is limited due to regular lack direct evidence. For instance, the rarity of many Gaucher patients in the general population makes it difficult for scientists and researchers to find enough patients with the Gaucher disorder of variants related to this disorder in order to do a traditional study. In response to this, an approach to providing guidance through decision modeling and establishment of a database that can aid in the collection and accumulation of evidence for Gaucher disorder on clinical utility and validity has been put in place (Levy-Lahad and Zimran, 1997). For instance, cohort studies have proved appropriate for evaluating clinical utility since they can precisely measure the capacity to detect or predict Gaucher disorder. Clinical validity evidence on Gaucher based on genetic testing can ideally be researched using controlled studies like RCTs. Nevertheless, the clinical utility and the amount of evidence needed to assess the clinical utility will be influenced by the particular clinical hint, the clinical setting as well as the professed value of possible results of the genetic testing.
In order to advance evidence based on genetic testing of Gaucher disorder various strategies have to be put in place. One way of doing this is by backing up high-quality studies of clinical utility and clinical validity. This can be done by including patient-centered results. Also, by implementing procedures for data collection, accumulation and analysis with genetic testing and supporting evidence-based systematic reviews of genetic tests can offer a significant boost to evidenced-based genetic testing and counseling for Gaucher disease.
Although Gaucher disorder cannot be cured various treatments can assist in controlling and generally improving its symptoms. However, genetic counseling is the most appropriate in the prevention of Gaucher disease if it is within a family history or in a population as a whole (Levy-Lahad and Zimran, 1997). Genetic counseling can be facilitated by conducting genetic testing by use of the procedures mentioned above. Once the carriers have been identified, the counselors can advise the patient on the available options on how to manage and prevent them from having Gaucher children. This will, therefore, prevent the spread and development of Gaucher disease among the population.
Reference
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Rosenbloom BE, Weinreb NJ. (2013). Gaucher disease: a comprehensive review. Crit Rev Oncog.Vol.18(3):163-75.
