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What is the primary cause of cystic fibrosis?
What is a consequence of the abnormal CFTR protein in cystic fibrosis patients?
Which organ systems are most adversely affected by cystic fibrosis?
How is cystic fibrosis inherited?
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What is the estimated frequency of cystic fibrosis in live births?
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What percentage of people with cystic fibrosis are 18 years of age or older?
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What is the primary consequence of defective chloride transport in cells?
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Which gene mutation primarily causes cystic fibrosis?
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Which test is primarily used to diagnose cystic fibrosis?
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Which of the following conditions is categorized as a rare disease (RD)?
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What characterizes Hutchinson-Gilford Progeria Syndrome (HGPS)?
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What is the estimated prevalence of Progeria in births?
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What non-pulmonary clinical manifestation is associated with cystic fibrosis?
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Which statement about the fertility of individuals with Progeria is correct?
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In cystic fibrosis, what effect does the disruption of chloride channels have on the organ systems involved?
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Which demographic characteristic is noted about children affected by Progeria?
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What is a limitation of hematopoietic stem cell transplantation in the treatment of MPS disorders?
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Which statement correctly describes enzyme replacement therapy for MPS I, II, and VI?
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What is the primary goal of tertiary prevention in caring for patients with MPS disorders?
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What aspect of patient care is emphasized for MPS patients due to the progressive nature of the condition?
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Which of the following complications is NOT mentioned as part of the multidisciplinary attention for MPS patients?
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Which mutation is commonly associated with classic HGPS?
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What is the primary gene involved in HGPS?
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What is a notable treatment option for managing cardiovascular conditions in children with HGPS?
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Which of the following statements about mucopolysaccharidoses is true?
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What is one function of glycosaminoglycans (GAGs) in the body?
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In the context of mucopolysaccharidoses, what is unique about Hunter disease?
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Which of the following is NOT a component of glycosaminoglycans (GAGs)?
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What is a possible benefit of using low-dose aspirin in children with HGPS?
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What roles do glycosaminoglycans (GAGs) play in the body?
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Which condition is characterized by absent or reduced activity of mutated lysosomal enzymes related to proteoglycans?
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Which of the following features is not typically associated with MPS I (Hurler Syndrome)?
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What is the inheritance pattern of MPS II (Hunter Syndrome)?
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Which enzyme is deficient in MPS VI (Maroteaux-Lamy Syndrome)?
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What is the purpose of enzyme replacement therapy in the treatment of MPS?
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Which of the following clinical features is unique to MPS III (Sanfilippo Syndrome)?
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Which of the following is a common characteristic across various forms of MPS?
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What physiological effect does enzyme replacement therapy not alleviate?
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What is a typical outcome of lysosomal disturbance in MPS conditions?
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Study Notes
Rare Diseases (RDs)
- RDs pose a long-term threat to health, some are disabling and fatal.
- Many RDs lack FDA approved drug treatments.
- RDs are referred to as "uncommon diseases" in Hong Kong, a definitive definition is lacking.
- Some common RDs include Mucopolysaccharidoses, Pompe Disease, Angelman Syndrome, Albinism, Marfan Syndrome, Rett Syndrome, Spinocerebellar Ataxia, Tuberous Sclerosis Complex, Spinal Muscular Atrophy, Fabry Disease, Retinitis Pigmentosa.
- The estimated total number of patients with RDs in Hong Kong is as high as 110,000.
Cystic Fibrosis (CF)
- CF is an autosomal recessive disorder affecting epithelial cells of the respiratory, gastrointestinal and reproductive tracts.
- CF is caused by a mutation in the CF gene on chromosome 7, encoding the cystic fibrosis transmembrane regulator (CFTR) protein.
- The abnormal CFTR protein disrupts chloride channels on cells, causing thick and sticky mucus secretion.
- CF primarily affects the lungs, leading to chronic obstructive pulmonary disease (COPD) in early adulthood.
- The frequency of CF is 1 in 2,000 to 3,000 live births, with approximately 30,000 children and adults affected in the United States.
- CF was once considered a fatal childhood disease, but approximately 38% of individuals with CF are now 18 years of age or older.
- CF manifests with gastrointestinal problems (e.g., pancreatic insufficiency), biliary cirrhosis, vitamin D deficiency, recurrent pancreatitis, and weight loss.
- Sweat test is used for diagnosis, with sweat chloride values greater than 60 mEq/L being indicative of CF.
- Genetic tests identify the type of CFTR defect.
- Chest x-ray can reveal inflated lungs, fibrosis, and scarring.
Progeria (Hutchinson-Gilford Progeria Syndrome, HGPS)
- Progeria is a rare, fatal genetic condition causing accelerated aging in children.
- The prevalence of HGPS is reported to be 1 in 8 million births, with a possible true prevalence closer to 1 in 4 million births due to underdiagnosis.
- Progeria affects all races with approximately 97% of cases occurring in Caucasians.
- Progeria affects both sexes almost equally, with a slightly higher prevalence in males (1.5:1 male-to-female ratio).
- Individuals with progeria typically experience severe growth failure, preventing fertility.
- Progeria is caused by a mutation in the LMNA gene leading to the production of a permanently farnesylated mutant prelamin A protein called progerin, causing nuclear architecture defects.
- Diagnosis is based on clinical features and molecular genetic testing of LMNA.
- Targeted mutation analysis can identify the specific LMNA mutation associated with HGPS.
- Treatments focus on managing cardiovascular disease, with low-dose aspirin, anticoagulants, and growth hormone being used.
Mucopolysaccharidoses (MPS)
- MPS are hereditary, progressive diseases caused by mutations in genes encoding lysosomal enzymes needed to degrade glycosaminoglycans (GAGs).
- GAGs accumulate in lysosomes, leading to cellular dysfunction and clinical abnormalities.
- MPS are autosomal recessive disorders except for Hunter disease, which is X-linked recessive.
- GAGs are long-chain complex carbohydrates containing uronic acids, amino sugars, and neutral sugars, playing roles as lubricants and shock absorbers.
- GAGs interact with proteins like proteases, growth factors, cytokines, chemokines, and adhesion molecules, influencing various physiological processes.
- Degradation of proteoglycans, composed of a protein core and GAG moiety, is disrupted in MPS, leading to GAG accumulation in lysosomes.
- MPS disorders are characterized by a specific pattern of clinical, radiologic, and biochemical abnormalities based on the specific degradation products accumulating.
MPS Symptoms
- MPS I (Hurler Syndrome): Coarse facial features, hepatosplenomegaly, corneal clouding, cognitive decline.
- MPS II (Hunter Syndrome): Coarse facial features, behavioral issues, mild cognitive impairment, hepatomegaly, joint stiffness.
- MPS III (Sanfilippo Syndrome): Severe neurological symptoms.
- MPS IV (Morquio Syndrome): Skeletal abnormalities, short stature, joint abnormalities.
- MPS VI (Maroteaux-Lamy Syndrome): Coarse facial features, short stature, organomegaly, skeletal abnormalities.
- MPS VII (Sly Syndrome): Dysmorphic features, organomegaly, dysmorphic features, severe neurological symptoms.
MPS Treatment
- Enzyme replacement therapy reduces organomegaly, sleep apnea episodes, and urinary GAG excretion, while ameliorating growth rate, joint mobility, and physical endurance.
- Enzyme replacement therapy is not effective for neurocognitive involvement as enzymes do not cross the blood-brain barrier.
- Hematopoietic stem cell transplantation significantly improves somatic disease in MPS I, II, and VI, preventing neurocognitive degeneration. However, it does not correct existing cerebral damage, skeletal or ocular anomalies.
- Treatment focuses on multidisciplinary care for respiratory, cardiovascular, hearing, carpal tunnel syndrome, spinal cord compression, and hydrocephalus complications.
MPS Prevention
- Primary prevention through genetic counseling.
- Tertiary prevention to avoid or treat complications through specialized and coordinated evaluation.
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Description
This quiz covers rare diseases, including their definitions and implications, along with a focused look at Cystic Fibrosis (CF), an autosomal recessive disorder. Learn about the impact of these diseases, common examples, and genetic factors involved. Test your knowledge on the critical aspects of RDs and CF.