Intro to metabolic disease Flashcards
def. metabolics
sum total of al chemical rxns in a cell which include ysnthesis and breakdown of organic molecules
what are diseases of metabolism
inborn errors of metabolism
what is basic chemical rxn
substrate>enzyme>product
what happens if no enzyme
incr. substrate and dec. product
what is basic PKU (phenyketonuria) rxn
phenyalalnine> phen. hydroxylase>tyrosine
what causes PKU
auto recessive due to mutation in PAH gene
prob. in PKU
- high phenylalanine
- low tyrosine leads low serotonin and dopa
- defective myelnation, cog. probs
what are sig. phenylalanine levels
normal - 120
- in PKU if can maintain 400 - near normal IQ
- each incr. of 300 leads to loss of 0.5SD of IQ
why are PKU light
tyrosine is also converted into melanin
what is PKU treatment
substrate reduction therapy - reduce all protein and take protein supplement
how is PKU tested for
all infants screened by tandem mass spectroscopy - used to be guthrie test
what is antoher PKU treatment
product replacement - give large AAs that compete for crossing over into brain of phenyalalnine
- reduces brain phenyl
- increased brain tyrosine and tryptophan
what is new PKU treatment
enzyme enhancement - BH4 - helps PAH
what is another new treatment
alternative routes of metabolism - PAL phenylalanine lyase turns Phe into cinammic acid
what are 3 main saccharides and makeup
maltose - glu +glu
lactose - glu + galactose
sucrose - glu + fructose
what is glycogne
highly branched polymer of glucose molecules
what causes glycogen storage disease
lack of glucose 6 phosphatase
- can’t create glucose from glycogen and gluconeogenisis to put into blood stream
phsyio effect of GSD
- low glocuse
- large liver with glycogen
- high triglycerides
- high lactate
clinical probs with GSD
- hepatomegaly
- hypoglycemia
- high triglycerides
- high uric acid
how to treat GSD
dependent on cornstarch feeds
what else needs to be managed
- fibrates for hyperlipiemia
- treat stones - ;ithroscopy
- monitor liver for adenomas
what is gene therapy for GSD
improvement of G6Pase activity and reduction of glycogen in liver
other therapy
hepatocyte transplant - may last up to a year
2 main types of metabolism disorders
- probs with intermediary metabolism
2. problems affectin organelles
what are organelle disease
conidtions involving macromolecules
how do organelle disorders present (3)
- pregressive
- permaent
- indep. of food intake
2 gen. clinical features of organelle dis.
- features correlate with organ where accumulation happens
2. features will affect organs where organelles are pref. utilized
what is lysozomal storage diseases
def. in one or more lysosomal hydrolases
- get substrate buildup
3 examples
- heparine sulfate - in brain
- dermatan sulfate - brain
- keratan sulfate - bone
what is mucopolysaccharidosis (MPS) type 1
hurlers syndrome
features of hurler
- runny nose and otitits
- hernias
- coarse face and cornela clouding
- large liver and spleen
- dev. slowed by year 2
what causes hurler
defect in iduonidase enzyme
what causes effects of hurlers
buildup and depends where it accummulates
3 treatments of hurler
- enzyme replacement therapy (ERT)
- bone marrow trnasplant (source of enzyme)
- treat syndromic complications
what is ERT effects for hurler
- improved joint ROM
- cardiac and pulm. function
- liver size reduced
what are limits of ERT (4)
- safelty - allergies common
- hard to reahc sx - brain
- know when to start/stop
- cost
when to do marrow trans
early and before IQ drops
3 reasons with think organelle
- regression
- chronic course
- dysmorphism
