Metabolic

Question 1

How is anion gap calculated and what is the normal range?

Answer 1

[Na+ + K+] - [Cl- + HCO3-]

Normal range 10-16 mmol/L

Question 2

Presentation of a baby with metabolic disease

Answer 2

Postnatal collapse
Floppy
Encephalopathy +/- seizures
Worse on feeding
May be genetic (usually recessive)
Increased risk in consanguinuity

Question 3

Metabolic conditions presenting with Respiratory alkalosis

Answer 3

High ammonia –> reduced CO2

Urea cycle defects
Ornithine transcarbamylase deficiency

Question 4

Metabolic conditions presenting with metabolic acidosis and raised lactate

Answer 4

• Mitochondrial
• Pyruvate disorders
• Glycogen storage disorders
• Organic acidaemias - Positive urine ketones

Question 5

Metabolic condition presenting with metabolic acidosis and normal lactate

Answer 5

Fatty acid oxidation defects
Urine ketones negative

Question 6

Presentation of organic acidaemias

Answer 6

Seizures / encephalopathy
Feeding difficulty / vomiting
Psychomotor retardation
Cardiomyopathy
Metabolic acidosis, normal lactate, +ve urine ketones

Question 7

Investigations and management of organic acidaemia

Answer 7

Ix: Metabolic acidosis with raised lactate
Raised ammonia
+ve urine ketones
Raised amino acid (specific to condition)

Tx:
IVF, diet control
Carnitine -renal excretion

Question 8

Presentation and management of galactosaemia

Answer 8

–> Unable to break down galactose, accumulates
Presentation:
- Jaundice
- Hepatomegaly
- Coagulopathy
- Cataracts
- Ix: urine reducing substances

Tx: dairy free diet, supplement calcium and vit D

Question 9

Presentation and management of glycogen storage disorder

Answer 9

Defect in enzyme involved in glycogenolysis eg Glucose-6-phosphate deficiency
Presents 3-4m when increased feeding intervals
- Hepatomegaly
- Hypoglycaemia
- Weakness / fatigue

Tx: Frequent feeding, ?liver transplant

Question 10

Presentation and mangement of homocystinuria

Answer 10

Cystathione beta synthase deficiency
Presents:
- Marfanoid
- DVT / PE
- OP
- Lens displacement
Tx: Dietary restriction methionine

Question 11

Presentation and treatment of MCADD

Answer 11

= Medium chain fatty acid oxidation disorder (needed for TCA cycle)
Presentation:
- Lethargy
- Low ketones, low glucose
- Encephalopathy
- Hepatomegaly
- High C8 levels on blood spot
- Raises octanoyl carnitine / urinary organic acids

Tx: Eat regularly, emergency glucose if unwell

Question 12

Presentation and treatment of Phenylketonuria (PKU)

Answer 12

Deficiency of phenylalanine hydroxylase –> build up of phenylalanine in blood and urine, not converted to tyrosine.
Presentation:
- Microcephaly
- Seizures
- GDD progressive
- Musty odour
- Raised phenylalanine

Dietary restriction phenylalanine, supplement other AAs eg tyrosine

Question 13

Presentation and management of urea cycle defects

Answer 13

Defect in enzymes that break down nitrogen –> urea for excretion. Build up of intermediate AAs. Eg citruillinaemia, OTC deficiency (x-linked).
Presents:
- Vomiting
- Encephalopathy
- Tachypnoea / resp. alkalosis due to build up ammonia
- GDD

Tx: Ammonia scavenging meds eg IV Argenine
Hold feeds, give glucose
Longterm - sodium benzoate, sodium phenylbutyrate
Protein restriction
Citrulline

Question 14

Presentation and management of mitochondrial disorders

Answer 14

Defect in Kreb’s cycle –> disrupted ATP supply.
Maternally inherited. Variable phenotype (heteroplasmy).
Presentation:
- Multisystem - esp brain, heart, kidney, retina, muscle
- RAISED LACTATE
- Leigh syndrome - changes to BG / brainstem

Tx: Ketogenic diet (fat heavy), thiamine

Question 15

What is Beutler test used in?

Answer 15

Galactosaemia

Question 16

What are Chvostek’s sign and Trousseau’s sign and what are they associated with?

Answer 16

Chvostek’s = tap facial nerve
Trousseau’s = Inflate BP cuff

HYPOCALCAEMIA