Metabol 5) Inborn errors of metabolism

Question 1

What are the management principles for inborn metabolic disorders?

Answer 1

Special diets
Peritoneal or haemodialysis
Administer deficient metabolite
Administer deficient enzyme
Administer cofactor or coenzyme
Activate alternative pathways
Bone marrow or liver transplant

Question 2

What categories of inborn metabolic disorders are there?

Answer 2

Amino acid disorders
Carbohydrate disorders
Lipid, fatty acid and organic acid disorders
Purine and pyramiding disorders
Haem disorders
Lysosomal storage disorders
Mitochondrial disorders
Peroxismal disorders

Question 3

Give examples of amino acid disorders

Answer 3

Transport disorders
 - dibasic amino acids (cystinuria)
 - neutral amino acids (Hartnup disease)
Metabolism
 - phenylalanine / tyrosine
 - urea cycle defects

Question 4

What is cystinuria?

Answer 4

Defective cystine transporter

Cystine in urine crystallises to form stones

Question 5

What is the management for cystinuria?

Answer 5

Symptomatic treatment
Prevent stone formation - water intake, alklaisation
Lithotripsy, chelation

Question 6

Describe the features of phenylketonuria

Answer 6

Normal at birth
Gradually develop neuropsychological problems
 - microcephaly, low IQ
 - seizures, tremor
 - impaired myelination
Blonde hair
Musty odour

Question 7

What is the management for phenylketonuria?

Answer 7

Diet
L-DOPA, 5-HT
BH4

Question 8

What are the signs of urea cycle defects?

Answer 8

Lethargy
Poor feeding
Seizures
Coma
Death

Question 9

What is the management for urea cycle defects?

Answer 9

Reduction of dietary protein intake
Removal of excess toxic products
Removal of excess precursors
Replacement of intermediates in urea synthesis 
Liver transplant

Question 10

Give examples of carbohydrate disorders

Answer 10

Glycogen storage disorders
 - liver - GSD-1
 - muscle - McArdle, Pompe
Galactose - galactosemia
Fructose - fructose intolerance
Gluconeogenesis
Pyruvate
Pentose

Question 11

What are the features of GSD-1?

Answer 11

Hypoglycaemia
Lactic acidosis
Lipidaemia
Hepatomegaly
Uricaemia
Neutropenia
Bruising
Renal disease

Question 12

What is the management of GSD1?

Answer 12

Continuous feeds or corn starch
Limit other sugars
Inhibit uric acid production
High cholesterol
Liver transplant

Question 13

What is galactosaemia?

Answer 13

GAL1PUT deficiency (galactose 1 phosphate uridyl transferase)

Question 14

What are the features of galactosemia?

Answer 14

Prolonged jaundice
Cataracts
Poor weight gain
Hepatomegaly

Question 15

What is the management of galactosemia?

Answer 15

Galactose free diet

Soy milk

Question 16

Describe MCAD deficiency

Answer 16

Hypoglycaemia when unwell or fasting
Unable to mobilise fatty acids and ketones when low glucose.
Reduced total carnitine, reduced free carnitine / acyl carnitine ratio
Elevated medium-chain acylcarnitines

Question 17

What is the management of MCAD deficiency?

Answer 17

Avoid fasting
Slow release carbohydrates
Supplement carnitine
Riboflavin

Question 18

What are lysosomes?

Answer 18

Spherical vesicles containing over 50 hydrolytic enzymes

Break down biomolecules

Question 19

What are the features of mucopolysaccharidoses?

Answer 19

Coarse facies
Mental retardation
Short stature
Contractures
Dysostosis
Multiplexa

Question 20

Give examples of mucopolysaccharidoses disorders

Answer 20

Hurler
Hunter
Sanfillippo

Question 21

Give examples of lipid storage disorders

Answer 21

Gangliosidosis
Tay sachs
Gaucher
Niemann-pick
Muclipidoses
Lipofuscinosis

Question 22

What are the consequences of mitochondrial disorders?

Answer 22

Respiratory chain defects

Brain, eye, heart and muscle problems

Question 23

Describe peroxisomal disorders

Answer 23

Production and decomposition of peroxide

Accumulation of VLCFA in adrenal glands and peripheral nerves