Biochem & Genetics Flashcards
Features of Lesch-Nyhan syndrome (purine salvage deficiency)
Intellectual disability Aggression, self-mutilation Orange "sand" in diapers (hyperuricaemia) Gout Dystonia
Treatment of Lesch-Nyan syndrome
Allopurinol, febuxostat (2nd line)
Clinical feature of Adenosine deaminase deficiency
Lymphotoxicity (one of major causes of AR SCID)
What is the defect and inheritance of Kartagener syndrome?
Defect: defective dynein arm -> immotile cilia
Inheritance: Autosomal recessive
Features of Kartagener syndrome
Infertility (immobile sperm, blocked fallopian tubes)
Ectopic pregnancy
Lung infections (bronchiectasis, recurrent sinusitis)
Ear infections
Conductive hearing loss
*Situs inversus
Four main types of collagen in the body (and what disease occurs when defective/deficient)
Type I (90%): Skin and bones (Osteogenesis imperfecta type 1)
Type II: Cartilage
Type III: Blood vessels (Vascular type of Ehler Danlos syndrome)
Type IV: Basement membrane (Defective in Alport syndrome, attacked by antibodies in Goodpasture syndrome)
What type of collagen is involved in would healing?
Granulation by type III collagen, later replaced by type I
Defect and inheritance of osteogenesis imperfecta
Defect: Decreased production of NORMAL type 1 collagen (problem forming triple helix), most common gene defect in COL1A
Inheritance: Autosomal dominant (most common)
Features of osteogenesis imperfecta
Multiple fractures with minimal trauma (or even during birth)
Blue sclera
Opalescent teeth
Hearing loss (abnormal ossicles)
Treatment of osteogenesis imperfecta
Bisphosphonates to reduce fracture risk
Defect and inheritance of Ehlers-Danlos syndrome
Defect: Faulty collagen synthesis (defective cleavage and cross-linking)
- Classical type: Mutation in type V collagen
- Vascular type: Mutation in type III collagen
Inheritance: Can be AD or AR
Features of Ehlers-Danlos syndrome
Hyper extensible skin
Joint hypermobility/joint dislocation
Easy bleeding/bruising
a/w berry and aortic aneurysms, organ rupture
Which vitamin is essential in collagen synthesis?
What happens if it is deficient?
Vitamin C!
Scurvy!
Defect and inheritance of Marfan syndrome
Defect: Defective fibrillin (FBN1 gene mutation on chromosome 15)
Inheritance: AD
Features of Marfan syndrome
Tall with long extremities, arachnodactyly (tapering fingers and toes)
High arch palate
Pectus carinatum/excavatum
Joint hypermobility
Lens subluxation
Aortic/mitral regurgitation
Aortic dissection and aneurysms (cystic medial necrosis)
Features of McCune-Albright syndrome
Unilateral cafe-au-lait spots with ragged edges
Polyostotic fibrous dysplasia (bone replaced by collagen and fibroblasts)
At least one endocrinopathy (e.g. precocious puberty)
Which copy of allele is deleted/mutated in Prader-Willi syndrome?
Paternal copy is deleted/mutated.
Maternal copy is imprinted/silenced - NORMAL
Which chromosome is does the gene deletion/mutation occur on in Prader-Willi and Angelman syndrome?
Chromosome 15
Features of Prader-Willi syndrome
Intellectual disability Obesity Hyperphagia Hypogonadism Hypotonia
Features of Angelman syndrome
Severe intellectual disability
Inappropriate laughter
Seizures
Ataxia
Which copy of allele is deleted/mutated in Angelman syndrome?
Maternal copy is deleted/mutated.
Paternal copy is imprinted/silenced - NORMAL
MELAS syndrome
1) What does it stand for?
2) What is its inheritance?
3) What does muscle biopsy show?
MELAS syndrome
1) Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
2) Mitochondrial inheritance (i.e. only mother pass to children, variable expression)
3) Ragged red fibers
Leber hereditary optic neuropathy
1) What is its inheritance?
2) What is its clinical feature?
Leber hereditary optic neuropathy
1) Mitochondrial inheritance
2) Bilateral vision loss in teens/young adults
What is the genetic defect and inheritance of cystic fibrosis?
Genetic defect: Mutation in CFTR gene on chromosome 7 (commonly a deletion in Phe508)
Inheritance: Autosomal recessive
