Disorders Flashcards
FHCM
Familial hypertrophic cardiomyopathy
1 in 500
Autosomal dominant
Enlargement of heart muscle, damage to mitral valve, arrythmia, fainting, shortness of breath
Mutation - single AA change in MYH7 gene which encodes beta myosin heavy chain (40% of cases)
Other mutations in Troponin I, Troponin T, alpha tropomyosin , alpha actin
MH
Malignant hypothermia
1 in 50,000
Pharmacogenetic disorder
Reaction to halothane and sevoflurane
Causes muscle contraction, incr metabolism, tachycardia, incr CO2, ACIDOSIS - lethal
Mutations in RYR1 gene causes it to become leaky in the presence of halothane/sevoflurane
Propofol doesn’t cause a reaction
CCD
Central core disease
Non progressive muscle weakness - difficulty with motor milestones, doing motor activities, muscle cells have central cores in them
Autosomal dominant or autosomal recessive
1 in 100,000
People with CCD often have MH
Mutation in RYR1 channel - causes it to be leaky so there is less Ca++ in the SR or else interferes with the interaction between DHPR and RYR1
CPVT
Catecholaminergic polymorphic ventricular tachycardia
Causes by mutation in the RYR2 gene.
Disrupts careful flow of Ca+ ions into cardiac muscle, generating an abnormal rhythm
ARVC
Arrythmogenic right ventricular cardiomyopathy
Mutation in RYR2 causes heart muscle to break down overtime increaing risk of arrythmia and sudden death
HOKPP
Hypokalemic periodic paralysis
Caused by a mutation in a subunit of DPHR encoded by CACNL1A3 gene
DHPR can’t sense voltage changes correctly - doesn’t cause Ca++ release from RYR1 - periods of paralysis
Can last between a few hours and a day.
Brody’s disease
Caused by mutations in SERCA
After periods of exercise/movement, especially in the cold, muscles become very stiff
Muscles of arms, legs and face affected (Usually eyelids )
Usually relax after a few minutes of rest
What causes Alzheimer’s?
Misfolded Beta amyloid protein causes insoluble plaques
Misfolded tau protein causes neurofibrillary tangles ( tau protein is in the microtubules in the brain
This disrupts the neurons in the brain
What causes creuzfeldt Jakob disease?
Misfolded prion protein (PrP) acts as a template for converting the non pathogenic alpha helix from to the pathogenic beta sheet form
Osteogenesis imperfecta
Abnormal bone formation in babies - bones break easily
Gly in collagen is replaced by an amino acid with a larger R group
This perturbs the normal helical structure of collagen
Blue sclera, fractures, deafness
Cystic fibrosis
Mutation in CFTR gene - delta F508, chromosome 7 (most common)
CFTR cannot get to proper place on cell membrane
Cl- ion absorption and secretion are regulated by the CFTR. If there is a mutation it leads to abnormal mucus
This causes breathing difficulty and lung infections
Hereditary haemochromatosis
Single base change 845G>A
Cysteine (TGC) -> tyrosine (TAC)
C282Y on chromosome 6
Hepcidin protein mutated
Hepcidin protein is responsible for regulating iron uptake into the blood
Too much iron in the blood - leads to organ damage, fatigue, joint pain, heart disease
Phenylketonuria (PKU)
Deficiency in enzyme phenylalanine hydroxylase (PAH) due to point mutation
PAH causes Phe-> Tyr
Phe accumulates and is converted to phenylketone/phenylpyruvate
If left untreated this can lead to problems with brain development ->mental retardation & seizures
Diet low in Phe and high in Tyr = treatment
Early detection is crucial since damage done is irreversible
Scurvy
Caused by insufficient hydroxylation of collagen
Vit C necessary to keep prolyl hydroxylase reduced & active
Collagen made in absence of prolyl hydroxylase is in sufficiently hydroxylated and can’t fold properly
Spots on skin, spongy gums, bleeding from mucus membranes
Niemann-Pick disease
Lysosomal storage disease
Sphingomyelin metabolism disorder
Autosomal recessive defect in gene encoding sphingomyelinase
Build up of sphingomyelin in brain, spleen, liver, lungs
Develops in infancy, leads to mental impairment and eventually death
1/150,000 to 1/250,000
