Inborn Errors of Metabolism (15)

Question 1

How common?

Answer 1

Individually rare, collectively significant health problem

Question 2

Genetic defects

Answer 2

Protein might be folded incorrectly, over/under expressed gene (can’t perform same function)

Question 3

Problems with metabolic pathways

Answer 3

Complete block in pathway (not compatible with life), each reaction is catalysed by enzyme (can block pathway if enzyme not produced, produce less endpoint and metabolite prior accumulate > toxic), can form new compounds (helps with diagnosis)

Question 4

Co-factors

Answer 4

Enzymes need co-factors to carry out functions

Question 5

Biochemical genetics

Answer 5

Study/investigation of primarily genetic disorders that affect the metabolic pathways of cells

Question 6

Accumulation of a toxin can occurs for example

Answer 6

Urea cycle (ammonia) and haem synthesis (porphyrins)

Question 7

Ammonia accumulation

Answer 7

Lethargy, poor feeding, vomiting, tachypnoea, convulsions, coma and death

Question 8

Acute porphyria

Answer 8

Severe abdominal pain, pain in chest, legs/back, constipation/diarrhoea, vomiting, insomnia, palpitations, increase bp, anxiety/restlessness, seizures, mental changes, breathing problems, muscle pain/tingling/weakness/paralysis, red/brown urine

Question 9

Photosensitive porphyria

Answer 9

Sensitivity to sun/artificial light, sudden painful erythema (reddening of skin), oedema, blisters that take weeks to heal, itching, fragile skin, increased hair growth, red/brown urine

Question 10

Energy deficiency due to

Answer 10

defects of fatty acid oxidation

Question 11

Fatty acid oxidation used for

Answer 11

Energy when glucose is spared, produces acetyl CoA which feeds into citrate cycle and ketone production

Question 12

Defect in fatty acid oxidation

Answer 12

Only present when unwell and need extra energy, can’t generate ketones > hypoglycaemia

Question 13

Androgen insensivity syndrome caused by

Answer 13

Defective receptors

Question 14

Phenotype of androgen insensitive syndrome

Answer 14

Healthy female, normal breast development, absent pubic hair, genetic male XY (ambiguous genitalia)

Question 15

Presentation of androgen insensitive syndrome

Answer 15

Primary amenorrhoea, infertility

Question 16

Treatment of androgen insensitivity syndrome

Answer 16

Surgical resection of residual gonads

Question 17

Inborn errors of metabolism diagnosis

Answer 17

Test body fluids for abnormal metabolites, measure enzyme activities, histochemical/immunochemical staining, DNA analysis

Question 18

Basic urine metabolic screen

Answer 18

Spot tests, organic acids, amino acids (TLC/automated aa analysis), sugar chromatography, oligosaccharides/sialic acids, mucopolysaccharides

Question 19

What is homocystinuria?

Answer 19

Disorder of methionine metabolism > increase in homocysteine and its metabolites in blood and urine

Question 20

Clinical effects of high homocysteine

Answer 20

Mental retardation, marfinoid habitus (resembles marfans), ectopica lentis (displacement of eye’s crystalline lens), osteoporosis, thromboembolism

Question 21

Organic acids intermediates in most metabolic pathways

Answer 21

Neurotransmitters, aa, carbohydrates, drugs, diet, cholesterol, micro-organisms, fatty acids, purines, pyrimidines

Question 22

Acidaemias

Answer 22

Defects in branched chain aa catabolism, further away from the parent aa less likely to accumulate

Question 23

Classic organic acidaemias

Answer 23

Propionic, isovaleric, methyl malonic acidaemia

Question 24

Pre-natal screening tests

Answer 24

Neural tube defects - maternal serum and amniotic fluid AFP (a-fetoprotein), ultrasound scan 16 weeks

Down syndrome
1st trimester - PAPA, HCG, nuchal translucency
2nd trimester - maternal serum AFP, HCG, inhibin and estriol
Test on ascent - free fetal DNA