Rare Diseases and Cystic Fibrosis Overview

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Questions and Answers

What is the primary cause of cystic fibrosis?

Environmental factors affecting lung function

Mutation in the CF gene located on chromosome 7 (correct)

Deficiency of the cystic fibrosis transmembrane regulator (CFTR) protein

Abnormal secretion of epithelial cells

What is a consequence of the abnormal CFTR protein in cystic fibrosis patients?

Reduced risk of developing lung diseases

Increased fluid secretion in the respiratory system

Disruption of chloride channels on epithelial cells (correct)

Enhanced respiratory efficiency

Which organ systems are most adversely affected by cystic fibrosis?

Neurological and circulatory systems

Endocrine and immune systems

Respiratory and gastrointestinal tracts (correct)

Musculoskeletal and integumentary systems

How is cystic fibrosis inherited?

Autosomal recessive inheritance Signup and view all the answers

What is the estimated frequency of cystic fibrosis in live births?

1 in 2,000 to 3,000 Signup and view all the answers

What percentage of people with cystic fibrosis are 18 years of age or older?

38% Signup and view all the answers

What is the primary consequence of defective chloride transport in cells?

Thick and viscous secretions Signup and view all the answers

Which gene mutation primarily causes cystic fibrosis?

Mutation in the CFTR gene Signup and view all the answers

Which test is primarily used to diagnose cystic fibrosis?

Sweat chloride concentration test Signup and view all the answers

Which of the following conditions is categorized as a rare disease (RD)?

Cystic fibrosis Signup and view all the answers

What characterizes Hutchinson-Gilford Progeria Syndrome (HGPS)?

It results in an accelerated aging appearance. Signup and view all the answers

What is the estimated prevalence of Progeria in births?

1 in 4 million Signup and view all the answers

What non-pulmonary clinical manifestation is associated with cystic fibrosis?

Biliary cirrhosis Signup and view all the answers

Which statement about the fertility of individuals with Progeria is correct?

Severe failure to thrive often prevents fertility. Signup and view all the answers

In cystic fibrosis, what effect does the disruption of chloride channels have on the organ systems involved?

Obstruction of glands and ducts Signup and view all the answers

Which demographic characteristic is noted about children affected by Progeria?

Slight male predilection Signup and view all the answers

What is a limitation of hematopoietic stem cell transplantation in the treatment of MPS disorders?

It does not correct existent cerebral damage. Signup and view all the answers

Which statement correctly describes enzyme replacement therapy for MPS I, II, and VI?

It has been associated with normalization of enzyme activity in serum. Signup and view all the answers

What is the primary goal of tertiary prevention in caring for patients with MPS disorders?

To avoid or treat complications. Signup and view all the answers

What aspect of patient care is emphasized for MPS patients due to the progressive nature of the condition?

Specialized and coordinated evaluation. Signup and view all the answers

Which of the following complications is NOT mentioned as part of the multidisciplinary attention for MPS patients?

Liver failure Signup and view all the answers

Which mutation is commonly associated with classic HGPS?

c.1824C>T (p.Gly608Gly) Signup and view all the answers

What is the primary gene involved in HGPS?

LMNA Signup and view all the answers

What is a notable treatment option for managing cardiovascular conditions in children with HGPS?

Regular monitoring for cardiovascular disease Signup and view all the answers

Which of the following statements about mucopolysaccharidoses is true?

They are caused by mutations affecting lysosomal enzymes. Signup and view all the answers

What is one function of glycosaminoglycans (GAGs) in the body?

Serve as lubricants or shock absorbers Signup and view all the answers

In the context of mucopolysaccharidoses, what is unique about Hunter disease?

It is X-linked recessive. Signup and view all the answers

Which of the following is NOT a component of glycosaminoglycans (GAGs)?

Amino acids Signup and view all the answers

What is a possible benefit of using low-dose aspirin in children with HGPS?

To prevent heart attacks and stroke Signup and view all the answers

What roles do glycosaminoglycans (GAGs) play in the body?

Mediation of protein function, cellular adhesion, and signaling Signup and view all the answers

Which condition is characterized by absent or reduced activity of mutated lysosomal enzymes related to proteoglycans?

Mucopolysaccharidoses Signup and view all the answers

Which of the following features is not typically associated with MPS I (Hurler Syndrome)?

Mild cognitive impairment Signup and view all the answers

What is the inheritance pattern of MPS II (Hunter Syndrome)?

X-linked recessive Signup and view all the answers

Which enzyme is deficient in MPS VI (Maroteaux-Lamy Syndrome)?

β-glucuronidase Signup and view all the answers

What is the purpose of enzyme replacement therapy in the treatment of MPS?

To reduce organomegaly and improve joint mobility Signup and view all the answers

Which of the following clinical features is unique to MPS III (Sanfilippo Syndrome)?

Severe neurological symptoms Signup and view all the answers

Which of the following is a common characteristic across various forms of MPS?

Short stature Signup and view all the answers

What physiological effect does enzyme replacement therapy not alleviate?

Intellectual disability Signup and view all the answers

What is a typical outcome of lysosomal disturbance in MPS conditions?

Distended lysosomes Signup and view all the answers

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.