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DISEASE
(hypertension) and gradually kidney failure developed separately by two US companies, develops. The involvement of the blood vessels of the heart and brain may lead to heart disease Corporation. Results of clinical trials held to (myocardial infarcts [heart attacks], heart failure date were made public at the recent American and disorders of the function of the heart Society for Human Genetics meeting held in valves) and brain disorders (strokes, seizures, Philadelphia, and suggest that these therapies brain haemorrhage, and personality changes).
Other features include arthralgia (painful joints),diarrhoea, weight loss and disturbed tempera- ture sensation. Intelligence is normal.
The advancing kidney disease is the main cause of death. If untreated, the average Herston Hospitals Complex, Queensland age of death in males is 41 years. Both thequality and duration of life have been improved by advances in dialysis and transplantation to treat the kidney disease; improved painmanagement using drugs such as phenytoin and carbamazepine; and general improvements Typical skin rash seen in patients affected by Fabry disease. Fabry disease is an ‘X-linked disorder’, Victorian Clinical Genetics Service, Victoria which means that females ‘carry’ the genes, butmales are affected. However, symptomatic female either no symptoms or much milder symptoms Photos reproduced courtesy of Dr. Eric Haan, Director, South Australian Clinical Genetics Service, in females is a whorl-like pattern in the lens Women’s and Children’s Hospital. of the eye. A special instrument called a When a male with Fabry disease has children(Diagram 2), he will pass on his XF chromosome containing the Fabry gene to all of his daughters measurement of the enzyme, α-galactosidase, who will all therefore be carriers. He will pass on in blood cells or cultured skin cells. In females his Y chromosome to his sons who will therefore the enzyme activity may be reduced but this test is not reliable. A more reliable test in females is direct testing of the change in the gene if it has been identified in affected males in the family. If gene testing is not available for the family then it may be necessary to In males, the diagnosis of Fabry disease is made measure the enzyme activity in hair roots. by measuring the level of α-galactosidase activity In carrier females some of the hair roots have in blood or cultured skin cells. Affected males very low α-galactosidase activity and some have very low enzyme activity and the test is normal. (see Diagnosis of affected males and However, this test is not reliable for the identi- The gene for Fabry disease was discovered in 1986.
All of our characteristics are controlled by If a particular change (‘mutation’) in the Fabry gene has been identified in an affected male, his called chromosomes and exist in every cell female relatives can be tested for their carrier status by specific gene analysis to determine the presence chromosomes, and two of these, the X and or otherwise of the mutation. This method offers a the Y, determine our sex. Females have an definitive result for the individual.
XX pattern and males an XY pattern. The gene for Fabry disease is located on the X Before the Fabry gene was isolated and mutations chromosome. Males have only one X chromo- responsible for the disorder were found, it was some, and if there is a mistake in any gene on often necessary to measure the enzyme activity the X chromosome, disease results. If a female in up to 100 individual hair roots to determine has the gene for Fabry disease on one of her carrier status for females. This is a time-consuming two X chromosomes this usually causes her and resource-intensive process, as enzyme activity no major problems as the back-up copy of in each hair root required measurement individu- the gene on the other X chromosome usually ally. With the identification of the gene, the compensates. Such a female is said to be a method of choice for identifying carriers for Fabrydisease is analysis of the mutation(s) identified in a Fabry-affected male within the family.
When a carrier female (Diagram 1) has children,she can pass on either the X chromosome with the Fabry gene (shown as XF) or the partner X chromosome. Her children therefore have Clinical trials to determine the effectiveness of a 1 in 2 or 50/50 chance of inheriting the gene enzyme replacement therapy as a treatment for from her. If the child is a girl she will have a Fabry disease are currently underway in Australia 1 in 2 chance of being a carrier. If the child and elsewhere. This form of therapy, where Reproduced courtesy of the NSW Genetic Education Programme. is a boy, he will have a 1 in 2 chance of being commercially manufactured α-galactosidase is affected. Overall, there is a 1 in 4 (or 25%) infused into patients every two weeks, is being ) • Genzyme Corporation (USA) • Transkaryotic Therapies, Inc. (USA)
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1. Describe the changes in renal and hepatic function and other biological changes that occur 2. Identify factors that must be considered when determining adult medication dosages. 3. Calculate adult drug dosages using appropriate methods. 4. Discuss problems that may be encountered in administering medications to adults. 5. Identify medication-related problems that may occur in adults. 6.

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INCIDENCE OF SEXUAL DYSFUNCTION DURING THE PERI- AND POSTMENOPAUSE From the literature it appears that the prevalence of sexual problems Sexual dysfunction in the in women is high, that the prevalence increases with age, and thatthe menopausal transition has a negative influence on sexuality [2- peri- and postmenopause 8]. The prevalences of sexual dysfunctions may be underestimatedin

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