34. Inborn Errors of Metabolism 1

Question 1

What are the metabolic consequences of impaired enzyme activity?

Answer 1

Deficiency of a product
Accumulation of substrate
Conversion to an alternative product

Question 2

What is PKU caused by?

Answer 2

Autosomal recessive disorder

PAH enzyme defect or defective synthesis of cofactor

Question 3

Clinical symptoms of PKU

Answer 3

Irritability
Vomiting
Seizures
Mental retardation by 4-6 months
Reduced melanin production
Eczema

Question 4

Management of PKU

Answer 4

Diet low in phenylalanine

Supplement with tyrosine

Question 5

What is tyrosinaemia caused by?

Answer 5

Deficiency in fumarylacetoacetate hydrolase

Accumulation of fumaryl acetoacetate in urine

Question 6

Symptoms of tyrosinaemia

Answer 6

urine has cabbage-like odour
Liver failure
Renal tubular acidosis (acid blood)

Question 7

Treatment of tyrosinaemia

Answer 7

Dietary restriction of phenylalanine and tyrosine

Nitisonone drug

Question 8

What is aciduria?

Answer 8

Accumulation of organic acids in blood and urine

Question 9

What does MCADD stand for?

Answer 9

Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency

Question 10

What is MCADD?

Answer 10

Disorder of fatty acid oxidation due to impaired break down of medium-chain fatty acids into acetyl-CoA

Question 11

Symptoms of MCADD?

Answer 11

Hypoketotic hypoglycaemia
Liver dysfunction
SID
Lethargy
Seizures
Coma
Intolerance to fasting

Question 12

What are the clinical manifestations of alkaptonuria?

Answer 12

Dark urine
Ochronosis: pigmentation of eyes and ears
Arthritis caused by calcification

Question 13

What is the defect in maple syrup urine disease?

Answer 13

Metabolism of leucine, isoleucine, valine

Question 14

What are the symptoms of maple syrup urine disease?

Answer 14

Progressive lethargy
Weight loss
Maple syrup odour to urine
Ketosis, coma, death

Question 15

What is the treatment of maple syrup urine disease?

Answer 15

Dietary restriction of branched chain amino acids

Question 16

What is the defect in homocystinuria?

Answer 16

Defect in cystathionine synthase
Accumulation of homocysteine in the urine
Methionine and metabolites elevated in the blood

Question 17

What are the symptoms of homocystinuria?

Answer 17

Cardiovascular disease
Deep vein thrombosis
Stroke
Mental retardation
Osteoporosis
Dislocation of lens

Question 18

What are the dibasic amino acids?

Answer 18

Cysteine
Ornithine
Arginine
Lysine

Question 19

Name 4 disorders of amino acid transport

Answer 19

Cystinuria
Lysinuric protein intolerance
Hartnup disease
Iminoglycinuria

Question 20

How does cystinuria present?

Answer 20

Cystine renal stones

Dibasic amino acids in urine

Question 21

What defect causes cystinuria?

Answer 21

Defective absorption of cystine and dibasic amino acids

Question 22

What is the treatment of cystinuria?

Answer 22

High fluid intake

Alkalisation of urine with sodium bicarbonate

Question 23

What is the clinical presentation of lysinuric protein intolerance?

Answer 23

Failure to thrive
Poor apetite
Protein aversion
Hyperammonaemia with progressive encephalopathy
Renal failure
Osteoporosis

Question 24

What defect causes lysinuric protein intolerance?

Answer 24

Impaired function of urea cycle and lysine deficiency

Question 25

What happens to the plasma in lysinuric protein intolerance?

Answer 25

Increased ammonia

Decreased Arg, Lys, Orn

Question 26

What happens to the urine in lysinuric protein intolerance?

Answer 26

Increased ARg, Lys, Orn

Question 27

What is the treatment of lysinuric protein intolerance?

Answer 27

Protein restriction

Citrulline replacement to enhance urea cycle