Flashcards in Inborn Errors of Metabolism (IEM) Deck (39)
How many people are affected by inborn metabolic diseases?
1:1-2000 live births.
-most present in childhood
What causes inborn metabolic diseases?
Genetic defects of metabolic pathways.
What type of genetics is concerned with genetic disorders that affect metabolic pathways?
How can enzyme deficiencies be problematic? (2)
-Less metabolite produced (deficiency)
-Accumulation of substrate (toxic)
What are the main mechanisms of metabolic diseases? (3)
-Accumulation of toxin
-Deficient production of essential metabolite
What substance accumulates in patients with urea cycle defects?
-ammonia is not converted to urea sufficiently
What are the main clinical effects of hyperammonaemia (^ammonia)?
What substance accumulates in porphyrias?
What pathway is blocked in porphyrias?
Blockage of haem production pathway.
Outline the haem production pathway.
What are the main 2 types of porhyrias?
What substrates are in excess in acute porphyria? (2)
What substrates are in excess in photosensitive porphyria? (3)
What are the possible signs of acute porphyrias?
-Severe abdominal pain
-Pain in chest//legs/back
What are the possible signs of photosensitive porphyria?
-Sensitivity to light
-Sudden painful erythema/oedema
-Fragile, itchy skin
-Increased hair growth
What is a symptom present in both acute and photosensitive porphyria?
What is a major defect of energy deficiency?
Defects in fatty acid oxidation.
>> crisis presentations
What is the general process of fatty acid oxidation?
>> fatty acid oxidation
>> acetyl coA
>>ketones (outside mitochondria) / TCA cycle
Where does the majority of fatty acid oxidation take place?
What is the effect of defects in fatty acid oxidation?
What can cause deficient production of essential metabolite/structural components?
What can deficient production of essential metabolite/structural components lead to?
Androgen insensitivity syndrome.
-due to defective receptors
What are androgens?
Males sex hormones.
What is androgen insensitivity syndrome?
Genetically male persons is resistant to male hormones.
>> female phenotype, but the genetic makeup of a man
How does androgen insensitivity syndrome usually present?
What is the general genetic make up of most metabolic diseases?
How are IEMs diagnosed?
-Investigation of symptomatic individuals
What tests are carried out on symptomatic individuals? (4)
-Body fluid for abnormal metabolites
-Measure enzyme activity
-Histochemical / immunochemical staining
What is amino acid TLC?
Amino acid thin layer chromatography.
-separates different AAs
Pre-natal screening; how are neural tube defects detected?
Pre-natal screening; what are the tests for Down syndrome?
-1st trimester; PAPA, HCG
-2nd trimester; maternal serum, AFP, HCG, inhibin
-Free foetal DNA (ascent)
What is homocystinuria?
An inherited disorder of the metabolism of the amino acid methionine.
>> decreased production of cysteine
What enzyme deficiency causes homocystinuria?
Cystathionine beta synthase.
What are the clinical problems of homocystinuria? (5)
What is hyperhomocysteinemia?
An abnormally high level of homocysteine in the blood.
-above 15 µmol/L
-5% of the population
What conditions have an increased incidence of hyperhomocysteinemia? (3)
-Peripheral vascular disease
-Coronary artery disease
What types of molecules are the intermediates in most metabolic pathways?
Low molecular weight organic acids.
What are the defects in classic organic acidaemias?
Defects in branched chain AA catabolism.
-AAs are not always increased when deficient catabolic enzyme