Metabolic Disorders

Question 1

Which disorders does the Guthrie blood spot test screen for?

Answer 1

Phenylketonuria, congenital hypothyroidism, cystic fibrosis, sickle cell disease, medium chain acyl-co-A dehydrogenase deficiency, maple syrup urine disease, isovaleric acidaemia, glutaric aciduria type 1, homocystinuria

Question 2

What is phenylketonuria?

Answer 2

Phenylalanine hydroxylase deficiency

Question 3

What is congenital hypothyroidism?

Answer 3

Dysgenesis or agenesis of the thyroid gland

Question 4

What is specificity?

Answer 4

The probability that someone without the disease will correctly test negative

Question 5

What is sensitivity?

Answer 5

The probability that someone with the disease will correctly test positive

Question 6

What is positive predictive value?

Answer 6

The probability that someone who tests positive actually has the disease

Question 7

What is negative predictive value?

Answer 7

The probability that someone who tests negative actually doesn’t have the disease

Question 8

Name an organic acidaemia

Answer 8

Propionic acidaemia, isovaleric acidaemia

Question 9

Describe the key clinical features of organic acidaemias

Answer 9

High urea and ketones, metabolic acidosis. May have a funny smell from organic acids

Question 10

How are organic acidaemias managed?

Answer 10

Low protein diet, acylcarnitine, and haemofiltration

Question 11

Name one of the nine urea cycle disorders

Answer 11

Ornithine transcarbamylase deficiency

Question 12

Describe the key clinical features of urea cycle disorders

Answer 12

High ammonia (>200uM) leading to encephalopathy and developmental delay. Respiratory alkalosis. Vomiting

Question 13

How are urea cycle disorders managed?

Answer 13

Low protein diet to stop urea formation

Question 14

Name two amino acidopathies

Answer 14

Maple syrup urine disease, phenylketonuria

Question 15

Describe the key clinical features of phenylketonuria

Answer 15

High phenylalanine, blue eyes, fair hair and skin, retardation

Question 16

Describe the key clinical features of glycogen storage disorders

Answer 16

Hypoglycaemia, lactic acidosis, hepatomegaly, developmental delay. High risk of hepatoblastoma

Question 17

Describe the key clinical features of galactosaemia

Answer 17

Cataracts, hypoglycaemia, neonatal conjugated jaundice

Question 18

How is galactosaemia managed?

Answer 18

Low lactose and galactose diet

Question 19

Name a fatty acid oxidation disorder

Answer 19

Medium chain acyl CoA dehydrogenase deficiency (MCADD)

Question 20

Describe the clinical features of MCADD

Answer 20

Hypoglycaemia, cardiomyopathy, rhabdomyolysis, low ketones

Question 21

How is MCADD screened for?

Answer 21

Blood acylcarnitine

Question 22

How is MCADD managed?

Answer 22

Regular carbohydrate

Question 23

What are the clinical features of peroxisomal disorders?

Answer 23

Poor feeding, seizures, retinopathy, hepatomegaly, mixed hyperbilirubinaemia

Question 24

What are the clinical features of glycosylation disorders?

Answer 24

Retardation, nipple inversion

Question 25

How are glycosylation disorders diagnosed?

Answer 25

Measure serum transferrins

Question 26

Name a lysosomal disorder

Answer 26

Tay Sachs disease

Question 27

Describe the clinical features of lysosomal disorders

Answer 27

Very slow progressing neuroregression, hepatosplenomegaly, cardiomyopathy

Question 28

How are lysosomal disorders diagnosed?

Answer 28

Urine mucooligopolysaccharides, WBC enzyme levels

Question 29

How are mitochondrial disorders diagnosed?

Answer 29

Muscle biopsy

Question 30

Describe the blood test results in mitochondrial disorders

Answer 30

High lactate and creatine kinase

Question 31

State three groups of metabolic disorders that lead to accumulation of toxins

Answer 31

Organic acidaemias, urea cycle disorders, aminoacidopathies

Question 32

State three groups of metabolic disorders that lead to reduced energy stores

Answer 32

Glycogen storage disorders, galactosaemia, fatty acid oxidation disorders

Question 33

State two groups of metabolic disorders that affect large molecule synthesis

Answer 33

Peroxisomal disorders, glycosylation disorders

Question 34

What are peroxisomal disorders?

Answer 34

Inability to catabolise very long fatty acids or produce bile acids