Autosomal recessive disorders Flashcards
King Tut reading assignment
pictures showed him having gynecomastia
no gynecomastia, craniosynosteses or Marfan found
accumulation of malformations in his family is evident, consanguinity between mom and dad
avascular bone necrosis + malarial infection are cause of death
walking impairment and malarial disease is supported by discovery of canes in tomb
Cystic fibrosis (general)
- most common fatal autosomal genetic disease in the white population
- affects the cells that produce mucus, sweat, saliva, and digestive juices.
- Normally, these secretions are thin and slippery
- In CF a defective gene causes the secretions to become thick and sticky
- Instead of acting as a lubricant, the secretions plug up tubs, ducts and passageways, especially in the pancreas and lungs.
CF genetic abnormality
q arm of chromosome 7
MC mutation is F508
3 base deletion which leads to absence of phenylalanine residue at postion 508 on CFTR position
Protein affected CF
membrane associated protein, CFTR
transmembrane chloride channel protein that line passageways of lungs, liver, pancreas, etc.
transports Cl ions across membrane of cells in these areas
H2O follows Cl
CF pathophys
normal CFTR allows chloride, and therefore water and other fluids across various cells (keeping fluid secretions thin and slippery)
mutations here result in preventing usual flow of Cl and H2O which makes thick and sticky mucus
mucus obstructs airways and glands– mucus is not cleared and lungs are highly susceptible to infection, pancreas ducts get clogged so malabsoprtion of nutrients and chronic malnutrition
CF is pleotropic…
CF mutations result in complex multisystem effects:
- respiratory
- pancreas
- genital
- glands
clinical manifestations of CF
respiratory failure is most dangerous
blockage of pancreatic secretions causes malabsorption of key vitamins
meconium ileus due to obstruction by viscid meconium (newborns)
expression and penetrance patterns of CF
pulmonary dz and respiratory issues account for 90% of deaths in CF patients
lungs are histologically normal at birth
HOw is CF diagnosed?
sweat test
high salt level in pts sweat glands indicates disease
high [Cl] in sweat confirms
CF TREATMENT
focused on GI and pulmonary areas
mantain nutritional status, prevent airway obstruction and pancreatic enzyme replacement
bronchodilators, abx for infections
postural drainage to correct lung plugging
lysosomal storage disorders
deficiency of lysosomal hydrolase causing lysosomal accumulation of sphingolipid substrate
causes an accumulation of whatever the lysozyme breaks down
inability to degrade glycosphinogolipids, essential component of cell membranes, results in accumulation and leads to neurodegenerative effects and organomegaly
Tay-Sachs (general)
autosomal recessive metabolic lysosomal storage disorder
common among Ashkenazi Jews
three types: infantile, juvenile, adult
Tay-Sachs
genetic abnormality
mutation of HEXA gene on chromsome 15
tay-sachs
protein affeted
HEXA codes for alpha subunit of enxyme B-hexosaminidase A (in lysosomes)
pathophys
Tay-Sachs
B-hex A degrades GM2 ganglioside
diminished enzyme - lysosomal accumulation of GM2 in CNS
after so much accumulation, these cells die causing neurodegeneration
