Metabolic

Question 1

How do you calculate anion gap and what is normal?

Answer 1

([NA+] + [K+]) - ([HCO3-] + [CL-])
Normal is 10-14

Question 2

What are the causes of metabolic acidosis with rasied anion gap?

Answer 2

Lactic acidosis
DKA
Poisoning with: salicylate, methanol, propylene glycol, iron, isoniazid, ethylene glycol
Renal failure
Acid producing metabolic disorders

Question 3

What are the causes of metabolic acidosis with normal anion gap?

Answer 3

Renal tubular acidosis
Addison’s disease
Acetozolamide use
Severe diarrhoea
Post-ureteric diversion into large bowel

Question 4

What are normal ammonia levels in neonates and children?

Answer 4

<100 µmol/L in neonates and <50 µmol/L thereafter

Question 5

What is the classic presentation of a urea cycle disorder?

Answer 5

Poor feeding, seizures and reduced GCS in 1-5 days of life

Question 6

What are the classic lab findings for urea cycle diorder?

Answer 6

+++ ammonia, high lactate
respiratory alkalosis (driven by ammonia)
plasma amino acids deranged

Question 7

How are urea cycle disorders inherited?

Answer 7

AR
Except OTC which is X-linked

Question 8

Urea cycle orders are differentiated according to which amino acids are deranged. What are the two commonest types (in exams) + what amino acids are raised?

Answer 8

OTC - high alanine glutamine, low araganine and citrulline. V high urine orthotic acid
Citrullinaemia- high alanine and glutamine, very high citrulline. Low ariginine urine othotic acid

Question 9

Citrullinaemia has what enzyme defect?

Answer 9

ASS

Question 10

What is the management for Urea cycle disorders?

Answer 10

Acute: NBM, 10% dextrose +electroyltes. Sodium benzoate + haemofiltration.
Lifelong low protein diet + ammonia scanvengers

Question 11

Define hypoglycaemia

Answer 11

A true blood glucose of <2.6 mmol/L.

Question 12

What presentation would make you think of glycogen storage disease 1 ?

Answer 12

Hypoglycaemia, raised lactate
hepatomegally

Question 13

Describe how glycogen storage disease 1 leads to hypoglycaemia

Answer 13

Deficiency of glucose-6-phosphatase therefore inability to mobilize glucose from glycogen or to utilize glucose from gluconeogenesis.

Question 14

Describe Glycogen storage disease V

Answer 14

deficiency of the myophosphorylase enzyme, which leads to reduced glycolysis in muscle fibres and reduced production of pyruvate.

Question 15

Describe Glycogen storage disease V present?

Answer 15

muscle pain and cramps and fatigue during brief, intense exercise a/w episodes of dark urine (myoglobin)

Question 16

Describe Leigh’s syndrome

Answer 16

Mitochondrial disease
Sub-acute sclerosing encephalopathy
Presented as 2-3 yr old with developmental delay/ seizure/ myopathy
Raised lactate and classic MRI findings

Question 17

What are the MRI findings for Leigh’s syndrome?

Answer 17

Symmetrical changes of the basal ganglia and the brainstem.

Question 18

How does MCAAD present?

Answer 18

Part of neonatal screening
Can present before with poor feeding, generally unwell and seizures and Hypoketotic hypoglycaemia.

Question 19

What is MCAAD a disorder of?

Answer 19

fatty acid oxidisation disorder
(Medium-chain acyl-CoA dehydrogenase )

Question 20

How is MCAAD diagnosed?

Answer 20

clinical picture + measurement of carnitine and acylcarnitine levels and urine organic acids

Question 21

What is treatment of MCAAD?

Answer 21

Avoid prolonged fasting and take extra calories when ill
Will otherwise have normal development and growth

Question 22

Describe idiopathic ketotic hypoglycaemia

Answer 22

Presenting in first few years with hypoglycaemia and ketones during intercurrent illness or prolonged fast. Treat with emergency glucose and avoid fasting.
resolves by 8 years of age
Diagnosis of exclusion - need all your ammino acids plasma and urinary and carntitne and acylcarnitine to be normal

Question 23

What are the lab findings of Galactosaemia?

Answer 23

Conjugated bilirubinaemia , deranged coag and metabolic acidosis, urinary reducing substances, glycosuria, aminoaciduria, albuminuria.

Question 24

Describe Galactosaemia, it’s mode of inheritance and how it usually presents

Answer 24

AR
Cannot metabolise galactose
Presents as jaundice, poor feeding, cataracts, e-coli sepsis

Question 25

What is the treatment for Galactosaemia?

Answer 25

Never have galactose
Manage cataracts
Girls infertile- see endocrine

Question 26

Describe homocystinuria

Answer 26

AR. In newborn screen
unable to metabolise methionine
Down and out lens dislocation, tall, ID, aortic and mitral valve regurg, pectus excavatum.
Needs plasma amino acid screen

Question 27

What is the treatment for homocystinuria?

Answer 27

Pyridoxine and B6, low protein diet.

Question 28

Describe Maple Syrup Urine Disease

Answer 28

In newborn screen
Presents as progressive encephalopathy + sweet piss. Often looks like sepiss

Question 29

Describe phenolketonuria

Answer 29

deficiency of phenylalanine hydroxylase, which converts phenylalanine to tyrosine.

Question 30

How do GLUT1 transporter disorders present?

Answer 30

early-onset epileptic encephalopathy resistant to standard anti-convulsant medications. Unrecognized, the patient suffers developmental delay and evolution of a movement disorder.

Question 31

Presance of urine succinylacetone is pathagnomic of what?

Answer 31

Tyrosinaemia type 1