In born errors in metabolism Flashcards
when do inborn errors in metabolism present
childhood.
mutation can result in
Protein function not present due to the destruction of its structure.
Over/ under expressed gene so too much or too little protein is made.
Blockage of any metabolic pathway can result in a disorder.
what molecules are co factors
vitamins
what is used to convert a reactant to it’s product
enzymes.
what molecule accumulates in a patient with urea cycle defects
ammonia
what are the clinical effects of hyperammonaemia toxicity
lethargy, poor feeding, vommiting, tahcypnoea, convulsions, coma and death.
porphyrins accumulate in porphyries what are the possible acute signs of acute porphyria.
Severe abdominal pain Pain in your chest, legs or back Constipation or diarrhoea Vomiting Insomnia Heartbeat you can feel (palpitations) High blood pressure Anxiety or restlessness Seizures Mental changes Breathing problems Muscle pain/tingling/weakness/paralysis Red or brown urine
signs of photosensitive porphyria
Sensitivity to the sun/artificial light Sudden painful erythema and oedema Blisters that take weeks to heal Itching Fragile skin Increased hair growth Red or brown urine
why does energy deficiency cause crisis presentations in defects of fatty acid oxidation
- Fats- used when energy is compromised from glucose e.g. fasting.
- Cannot see fatty acid defects unless you get ill e.g. viral infection
what effect does inborn errors in metabolism have if they cause a non functioning androgen receptors
Androgens are male sex hormones which typically bind to specific receptors.
male genotype but not phenotype.
what is the phenotype of a patient with inborn errors in metabolism of androgen receptors.
healthy female phenotype normal breast development absent pubic hair, genetic male
what is the presentation of a patient with inborn errors in metabolism of androgen receptors.
primary amenorrhoea, infertility
do the same in born errors in metabolism have different penetrance
Yes
how are in born errors in metabolism diagnosed
Pre-symptomatic screening
whole population.
Investigation of symptomatic individuals.
• test body fluids for abnormal metabolites
• measure enzyme activities
• histochemical / immunochemical staining
• DNA analysis
Basic urine metabolic screen • Spot tests • Organic acids • Amino acids • Sugar Chromatography • Oligosaccharides/Sialic Acids • Mucopolysaccharides
define in born errors in metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products)
what are the clinical problems of homocystinuria
- Mental retardation
- Marfinoid habitus (marfan sydrome)
- Ectopia lentis (displacement or malposition of the eye’s crystalline lens)
- Osteoporosis
- Thromboembolism
what causes increased incidence of hyperhomocystinaemia
stroke
PVD-peripheral vascular disease
coronary artery disease.
small molecular weight organic acids are intermediates in mot metabolic pathways.
organic acids include
amino acids, neurotransmitters, carbohydrates, micro-organisms, fatty acids, purines and pyrimidines, cholesterol, drugs and diet.
organic acidaemias are defects in what types of amino acids
branched chain amino acid
Benefits to diagnosis of inborn errors in metabolism
Treatment, improve prognosis-cannot treat fully but can increase quality of life.
Identify cause of clinical problem- so patient knows what they have and doctor can start clinical examinations
Genetic counselling- most are recessive so ¼ chance of child with it.
IEM act as models for other disorders- biochemistry behind the disorder so you can treat it.
Pre natal screening tests
Neural tube defects
• maternal serum and amniotic fluid AFP
• ultrasound scan at 16 weeks
Down syndrome
• 1st trimester; PAPA, HCG and nuchal translucency
• 2nd trimester, maternal serum AFP HCG, inhibin and estriol
• Test on the ascent: free fetal DNA
how do in born errors of metabolism lead to disease
accumulation of toxin
energy deficiency
deficient product of essential metabolites/ structural component.
define homocystunuria
inability to metabolise amino acid homocystine.
classic acidaemias
propioni, isovaleric, methyl malonic academia.
define MSUD
maple syryp urine disease
aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration in untreated infants.
How can MSUD be treated
diet
If you have a urea cycle defect what can be seen on amino acid testing
arginionsuccinic acid
