Biochem14 Flashcards
Autosomal Recessive Diseases
List the autosomal recessive diseases.
Albinism ARPKD Cystic fibrosis Glycogen storage diseases Hemochromatosis Mucopolysaccharides (Except Hunter's) Phenylketonuria Sickle cell anemias Sphingolipidoses (Except Fabry's) Thalassemias
What is the gene/chromosome and common deletion in Cystic Fibrosis?
What does this cause cellularly?
CFTR gene on Chr 7
deletion of Phe 508
Abnormal protein folding –> degradation of channel before reaching cell surface
What is the normal function of the CFTR channel?
Secretes Cl- in Lungs & GI tract
Reabsorbs Cl- from sweat
Why are males steril in Cystic fibrosis?
Bilateral absence of vas Deferens
The defective Cl- channel in CF leads to a what?
secretion of abnormally thick mucus that plugs the lungs, pancreas, and liver.
Recurrent pulmonary infections
What type of bacteria cause the recurrent pulmonary infections in CF?
Pseudomonas & S. aureus
Newborns with CF have what finding?
Meconium ileus
T/F - Cystic fibrosis is the most common lethal genetic disease of the white population
True
What is diagnostic for CF?
INcreased concentration of Cl- in sweat test
What is the treatment for CF?
MOA?
N-acetylcysteine
Loosens mucous plugs by cleaving disulfide bonds within mucous glycoproteins
What is the mnemonic for the X-linked Recessive disorders?
Be Wise, Fool’s GOLD Heeds Silly HOpe
B - Bruton's agammaglobulinemia W - Wiskott-Aldrich syndrome F - Fabry's disease G - G6PD deficiency O - Ocular albinism L - Lesch-Nyan syndrome D - Duchenne's (and Beckers) muscular dystrophy H/S - Hunter's Syndrome H - Hemophilia A and B O - Ornithine transcarbamoylase deficiency
Why do females have much less severe symptoms in X-linked recessive disorders?
Random X chromosome inactivation in each cell
What type of mutation is seen in Duchenne’s muscular dystrophy?
X-linked FRAMESHIFT mutation –> deletion of dystrophin gene –> accelerated muscle breakdown
Where does weakness begin in DMD?
Pelvic girdle muscles – moves superiorly
What causes the pseudohypertrophy of calf muscles seen in DMD?
fibrofatty replacement of muscle
What is a characteristic sign of a child with DMD?
Gower’s sign
assistance of upper extremities to stand up
What is the onset of DMD?
Before age 5
What is the function of Dystrophin?
Helps anchor muscle fibers (skeletal & cardiac)
How do you diagnose DMD?
INcreased CPK & Muscle biopsy
What is the onset of age in Becker’s muscular dystrophy?
Adolescence or early adulthood
What does the X-linked defect in Fragile X syndrome cause?
Methylation and expression of the FMR1 gene
What are the clinical findings in Fragile X syndrome?
Macroorchidism (big balls) Long face w/ large jaw large everted ears Autism Mitral valve prolapse
“Fragile X = eXtra large testes, jaw, ears”
What is the 2nd most common genetic cause of mental retardation ?
Fragile X syndrome (1st - downs)
What are the Trinucleotide repeat expansion diseases?
“TRY (trinucleotide) HUNTING for MY FRIED EGGS (X)”
Huntington’s Dz
Myotonic dystrophy
Friedreich’s ataxia
Fragile X syndrome
