inborn errors of metabolism 1 Flashcards
Explain the genetic basis of IEMs and modes of inheritance
Inborn Errors of Metabolism - genetic disorders mostly involving single genes which code for enzymes involved inmetabolic pathways or transport proteins - clinical presentations usually arise due to accumulation of toxic substances or deficiency of product of metabolic pathway
discuss the mtabolic consequences of impaired enzyme activity (IEM)
in an impaired enzyme situation
- accumulation of substrate
- deficiency of product
- diversion to alternate product
list the categories of IEMs and discuss general clinical characteristics
Group 1= disorders which give rise to intoxication - accumulation of a toxic compound (PKU, MSUD, Organic acidurias) - generally they do not interfere with fetal development, most treatable with removal of toxin
Group 2= disorders involved in energy metabolism - IEM of intermediary metabolism and symptoms arise due to energy deficiency
Group 3= disorders involving complex molecues - involves cellular organelles including diseases associated with disturbed synthesis or catabolism of complex molecules (lysosomal storage disorder, etc)
What is phenylketouria?
(Hyperphenylalaninaemia) -
deficiency of phenylalanine hydroxylase - so phenylalanine is made into phenylketones in the urine instead of making Tyrosine
these phenylketones can build up to highly toxic levels resulting in damage
what is tyrosinaemia?
increased plasma concentration of tyrosine
what is homocystinuria?
defect in cystathionine synthase - accumulation of homocysteine in the urine - methionine and metabolites elevated in the blood.
leads to mental retardation, osteoporosis, myocardial infarction and dislocation of the lens =
what is maple syrup urine disease?
caused by a defect in the metabolism of leucine, isoleucine and valine - (deficiency in alpha keto acid dehydrogenase)
treatment = dietary restriction of branched chain amino acids
discuss hyperammonaemia and disorders of the urea cycle including OTC deficiency
hyperammonaemia = high levels of ammonia in the blood which can be neurotoxic to CNS -
OTC deficiency leads to hyperammonaemia - due to deficiency of ornithine transcarbamylase enzyme
describe the principles of newborn screening to detect inborn errors of metabolism
early detection of rare inherited conditions, before the onset of any clinical manifestations and the early introduction of treatment leads to better clinical outcome and avoids significant morbidity
we screen for (all of which ireland has a higher incidence of)
phenylketonuria
homocystinuria
maple syrup urine disease
classical galactosaemia
congenital hypothyroidism
cystic fibrosis
What is Alkaptonuria?
deficiency in homogentisic acid oxidase
you see pigmentation of ears and eyes to a grey color