B: Diseases Flashcards
Niemann-Pick disease:
- lysosomal storage disease caused by autosomal recessive genetic defect in gene for sphingomyelinase.
- Results in a build up on sphingomyelin in brain, spleen, liver and lungs.
Tay-Sachs disease
- lysosomal storage disease.
- Progressive deterioration of nerve cells + mental and physical capabilities.
- Autosomal recessive,
- build up of gangliosides in brain due to mutations in HEXA gene that codes for hexosaminidase A enzyme that catalyses degradation of gangliosides.
Battens disease
- Due to a build up of lipofuscins
- Defect in CLN3 gene that codes for battenin protein
Familial hypertrophic cardiomyopathy: —
Heart muscles enlarge, causing walls of ventricles to thicken + block blood flow. Can also cause blood to leak backwards through mitral valve.
Caused by change of amino acid in myosin protein due to a missense mutation (replacement of one amino acid with a different amino acid) in MYH7 gene.
Malignant hyperthermia —
RYR1 Ca++ release channel is leaky - calcium leaks out of SR onto myofibril causing increased contracture - consumes ATP and generates heat.
When anaesthetics are given to patient, there is a rapid increase in body temperature + metabolism + contracture of skeletal muscle. Increase metabolism causes tachycardia + increase CO2 production which can lead to acidosis.
Central Core Disease (CCD) —
RYR1 Ca++ release channel is leaky- lower concentration of Ca in SR and higher basal level of Ca in myoplasm.
Muscle weakness disorder.
Hypokalemic period paralysis —
Mutation in one of the subunits of DHPR –> defective in sensing depolarisation so cannot activate ryanodine receptor efficiently. This leads to attacks of muscle weakness/ paralysis
Brody’s disease —
Mutation in Ca++ ATPase –> causes muscle cramping and stiffening after exercise + strenuous activity.
Phenylketonuria (PKU)
Deficiency in phenylalanine hydroxylase (PAH)
- PAH metabolises Phe to Tyr
- Phe accumulates –> converted to phenylpyruvate
- Left untreated –> problems with brain development, mental retardation, seizures
- no cure
Scurvy
Insufficient hydroxylation of collagen
- Ascorbic acid + vitamin C keep prolyl hydroxylase reduced
- Collagen synthesised in absence of ascorbic acid = insufficiently hydroxylated –> can’t fold properly
- Spots on skin, spongy gums, bleeding from mucous membranes
Alzheimer’s
Formation of spontaneously aggregated (misfolded) B-amyloid
- Accumulation of plaques of insoluble B-amyloid in brain
Creutzfeldt-Jakob disease
Misfolded PrP (prion protein) –> acts as template for converting normal protein to a pathogenic B-sheet form
Osteogenesis imperfecta
Perturbed collagen structure –> due to a single amino acid change of Gly to an amino acid with a larger R group
- Abnormal bone formation in babies
Cystic Fibrosis
Defects in a chloride channel (CFTR)
- 2 mutated copies of the CFTR gene causes misfolding of the CFTR protein and its blocking in the Endoplasmic reticulum
- Breathing difficulties, lung infections due to abnormal mucus
Hereditary Haemochromatosis (Celtic Curse)
Can’t control levels of iron –> damage to vital organ over long period of time due to build up of iron free radicals
- Hfe = gene most commonly implicated
- C282Y = most common mutation of Hfe –> perturbs transport of Hfe protein (critical for iron metabolism) to the cell surface
