Chem path 6s - Metabolic disorders 2

Question 1

What are two key features of urea cycle disorders?

Answer 1

Hyperammonia and respiratory alkalosis

Question 2

What mode of inheritance do urea cycle disorders tend to have?

Answer 2

Autosomal recessive, hence there isn’t often a family history

Question 3

Which urea cycle disorder does NOT have an AR inheritnece?

Answer 3

Ornithine transcarbamylase deficiency - it is X-linked

Question 4

How do you detect urea cycle defects?

Answer 4

The body usually removes ammonia as it is toxic but it is unable to remove such high levels of ammonia, it instead attaches an ammonium group to glutamate –> glutamine.

• Serum glutamine is high
• Serum amino acids in urea cycle will either be HIGH or ABSENT
• Urine orotic acid

Question 5

How do you treat urea cycle disorders?

Answer 5

Remove ammonia (sodium benzoate, sodium phenylacetate or dialysis)
Reduce ammonia production (low protein diet to stop urea formation)

Question 6

What long term condition can be an indicator of urea cycle disorders?

Answer 6

Long-term psychiatric conditions

Question 7

What are the key features/ symptoms of patient with urea acycle disorder?

Answer 7

Resp alkalosis
Hyperammonaemia
N+V
Vomiting without diarrhoea
Neurological encephalopathy
Avoiding/change in diet

Question 8

What is a metabolic acidosis + hyperammonaemia + high anion gap suggestive of?

Answer 8

organic aciduria

Question 9

What are the three branch chained amino acids?

Answer 9

Leucine, Isoleucine and valine

Question 10

What are organic acidurias often associated with?

Answer 10

Funny smelling urine e.g. cheesy or sweaty, due to the organic acids

Question 11

What is an example of an organic aciduria?

Answer 11

Isovaleric acidaemia

Question 12

Which enzyme is deficient/absent in isovaleric acidaemia?

Answer 12

Isovaleryl coA-dehydrogenase

Question 13

How do organic acidurias generally present in neonates?

Answer 13

Unusual odour
Lethargy
Feeding difficulty
Truncal Hypotonia/ limb hypertonia
Myoclinic jerks
pancytopaenia
Neutropaenia
Thrombocytopaenia
Hypocalcaemia

Question 14

What are the features of the chronic intermittent form of organic acidurias?

Answer 14

Recurrent episodes of ketoacidotic coma
Cerebral abnormalities
Reye syndrome

Question 15

What is Reye syndrome?

Answer 15

Swelling of the liver and brain

Question 16

What coudl trigger Reye syndrome?

Answer 16

Salicylates, antiemetics, valproate, symptom of metabolic disease

Question 17

What is the Reye syndrome metabolic screen?

Answer 17

Plasma ammonia
Plasmia/urine amino acids
Urine organic acids
Plasma glucose and lactate
Blood spot carnitine profile

NOTE: The top 4 investigations should be performed during the acute state because the abnormal metabolites will disappear after a few days. Blood spot carnitine profile is the only measure which remains abnormal during remission!!

Question 18

What do mitochondrial fatty acid Beta oxidation defects present with?

Answer 18

hypoketotic hypoglycaemia (unable to make ketones as unable to break down fatty acids)

Also presents with hepatomegaly and cardiomyopathy

Question 19

What investigations would yu do for some one with mitochodnrial fatty acid beta oxidation defects?

Answer 19

Blood ketones
Urine organic acids
Blood spot acylcarnitine profile

Question 20

Name two carbohydrate disorders

Answer 20

Galactosaemia and Glycogen storage disorder type 1 (von Gierke’s)

Question 21

Most common galactosaemia

Answer 21

Galactose-1-phosphate uridyl transferaste (Gal-1-PUT) deficiency

Question 22

What does Gal-1-PUT deficiency lead to high levels of?

Answer 22

Gal-1-phosphate levels

Question 23

What do high Gal-1-phosphate levels lead to?

Answer 23

Liver and kidney disease, bilateral cataracts, also inhibits the immune response

Question 24

What does Gal-1-PUT deficiency present with?

Answer 24

D&V
Hypoglycaemia
cBr + hepatomegaly
Sepsis

Question 25

What are the investigations for galactosaemia?

Answer 25

HIgh urine galactose

Red cell Gal-1-PUT

Question 26

What is the treatment for galactosaemia?

Answer 26

Avoid galactose e.g. milk

Question 27

What is glycogen storage disorder type-1 (von gierke’s) a deficiency of?

Answer 27

Glucose-6-phosphatase deficiency

Question 28

What are the features of a glycogen storage disorder?

Answer 28

Hepatomegaly
Nephromegaly
Lactic acidosis
Hypoglycaemia
Neutropenia

Question 29

When should you consider mitochondrial disorders as a diagnosis?

Answer 29

If a disease affects multiple systems, particularly those with high energy requirements e.g. brain, muscle, kidney, retina, endocrine organs . mitochondrial disease can present at any age, in any organ with any mode of inheritance.

Question 30

Name 3 examples of mitochondrial disorder, when they present and how

Answer 30

Birth - Barth (Cariomyopathy, myopathy, neutropenia)
5-15y - MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes)
12-30 Kearns-Sayre - Chronic progressive external ophthalmoplegia, retinopathy, deafness, ataxia

Question 31

What investigation is diagnostic of mitochondrial disordesr?

Answer 31

Muscle biopsy - ragged red fibres

Question 32

What is another investigation done in mitochondrial disorders?

Answer 32

High lactate (alanine) especially when fasting or after meals. In normal people, lactate should be lower after fasting.

Question 33

What are some features of congenital glycosylation disorders?

Answer 33

Fat pads, nipple retraction and retardation

Question 34

What investigation is done in congenital glycosylation disorders?

Answer 34

Serum transferrin

Question 35

What is an example of a lysosomal storage disease and what are the features?

Answer 35

Tay Sachs

Neuroregression and dysmorphism

Question 36

What investigations are done for lysosomal storage disorders?

Answer 36

Urine mucooligopolysaccharide and WBC enzyme levels