Metabolic

Question 1

Hypokalaemic metabolic alkalosis
Hypercalciuria
Raised renin, aldosterone and prostaglandin E

Answer 1

Bartter syndrome

Question 2

When does maple syrup urine disease present?

Answer 2

First week of life (breastfeeding can delay onset until second week)

Question 3

Presenting symptoms of maple syrup urine disease?

Answer 3

Lethargy
Irritability
Poor feeding
Focal neurology - abnormal movements and increasing spasticity
Opisthotonus
Convulsions + coma

Question 4

What is the unique finding in maple syrup urine disease?

Answer 4

Characteristic maple odour in urine and earwax within a day or two of birth

Question 5

How do you confirm a diagnosis of maple syrup urine disease?

Answer 5

Raised amino acids (leucine, isoleucine, valine)

Question 6

How does galactosaemia present?

Answer 6

First 2 weeks of life
Poor feeding
Vomiting
Jaundice
Hepatomegaly

Question 7

How does methylmalonic academia present?

Answer 7

Few months into life
Neurological manifestations
Abnormally high methylmalonic acid in blood and urine

Question 8

How does PKU present?

Answer 8

In infancy
Lethargy
Feeding difficulties
Unusually light eyes, skin and hair
Musty odour
Eczematous rash
Developmental delay

Question 9

Biochemical findings in urea cycle defects?

Answer 9

Raised ammonia

Abnormal levels of intermediate molecules of the urea cycle (arginine, citrulline, others)

Question 10

How to treat acute illness in urea cycle defect with high ammonia?

Answer 10

Stop feeds (Take away protein load)
IV 10% dextrose
Remove ammonia with sodium benzoate

Question 11

Cause of Hunter’s disease

Answer 11

Deficiency of lysosomal enzymes that degrade GAGs, causing accumulation and excessive urinary excretion of GAGs

Question 12

Features of Hunter’s disease

Answer 12

Coarsening facies
Developmental delay
Heart murmur
Hepatomegaly
Joint stillness
Inguinal hernias
Short stature
Hydrocephalus

Question 13

Investigations in suspected Hunter’s disease

Answer 13

Echo
Urinary GAGs
Enzyme studies
Skeletal X-rays

Question 14

What is Hunter’s disease also known as?

Answer 14

MPS type II

Question 15

Cause of vitamin D dependent rickets type 1

Answer 15

Mutation in gene for enzyme 1 alpha-hydroxylate; therefore 1,25 vit D is low

Question 16

Treatment of vitamin D dependent rickets type 1

Answer 16

High dose vitamin D or 1 alpha-calciferol

Question 17

Diagnosis of rickets with raised or normal ALP, normal 1,25 fit D and low 25-hydroxycholecalciferol?

Answer 17

Nutritional rickets

Question 18

Cause of Gaucher’s disease

Answer 18

Glucocerebrosidase deficiency

Question 19

Most common lysosomal storage disease?

Answer 19

Gaucher’s

Question 20

Typical presentation of Gaucher’s

Answer 20

Tiredness
Organomegaly
Bone pain

Question 21

Diagnostic test for Gaucher’s

Answer 21

Enzyme studies

Question 22

Investigations that should be done in suspected Gaucher’s

Answer 22

Bone marrow aspirate
Leg X-ray
Ultrasound abdomen

Question 23

What will a bone marrow aspirate find in Gaucher’s?

Answer 23

Classic glycolipid-laden macrophages

Question 24

What will a leg X-ray show in Gaucher’s?

Answer 24

Erlenmeyer flask deformities

Question 25

When do you see microcytic anaemia with hyperhsegmented neutrophils?

Answer 25

Folic acid or B12 deficiency

Question 26

``` Global delay Microcephaly Muscular hypotonia External ophthalmoplegia Elevated lactate ``` Suggests?

Answer 26

Mitochondrial disease

Question 27

Cause of mitochondrial disorders?

Answer 27

Defects in the respiratory chain (complexes I to V) which are involved in producing cellular ATP

Question 28

Strongly consider a mitochondrial disorder in patients with:

Answer 28

Muscular disease + involvement of 2 additional systems CNS disease and involvement of 2 additional systems Multisystem disease (at least 3 systems) and involvement of muscle and/or CNS

Question 29

Initial investigations in suspected mitochondrial disease?

Answer 29

Organic acids CSF lactate MRI brain Muscle biopsy

Question 30

Presentation of MCADD

Answer 30

First 3 years of life Hypoglycaemia Hepatomegaly Sudden death, possibly brought on by a period of fasting or vomiting

Question 31

Blood tests in MCADD

Answer 31

Low bicarb Anion gap Hypoglycaemia in absence of ketons Mild to moderately high ammonia

Question 32

Blood tests in organic acidurias

Answer 32

Metabolic acidosis with ketosis Elevated lactate Mild to moderate hyperammonaemia

Question 33

What do reducing substances in the urine suggest?

Answer 33

Galactosaemia

Question 34

Most reliable test for galactosaemia?

Answer 34

Galactose-1-phosphate uridyltransferase in the blood

Question 35

Presentation of infantile Tay-Sachs disease

Answer 35

``` Ashkenazi Jewish 3-6 months Mild muscle weakness Myoclonic jerks Exaggerated startle response ```