Metabolic Disorders and Screening 2

Question 1

What is the overall function of the urea cycle?

Answer 1

Take ammonia

Produce urea

Question 2

What occurs when the urea cycle malfunctions (due to enzyme deficiency)?

Answer 2

HIGH AMMONIA

ammonia is very toxic

Question 3

What is the mode of inheritance for urea cycle disorders?

Answer 3

Most are autosomal recessive

ONE X linked disorder: OTC deficiency

Question 4

What is produced by the body when ammonia quantity is high?

Answer 4

GLUTAMINE
because ammonia binds to glutamate to make glutamine
this is part of the body’s attempt to excrete ammonia

Question 5

What can you measure to detect urea cycle defect?

Answer 5

Glutamine

Urine orotic acid

Question 6

How do you treat urea cycle defect?

Answer 6

FIRST LINE: remove ammonia using sodium benzoate / sodium phenylacetate

AFTERWARDS: reduce ammonia production via low protein diet

Question 7

What are key clinical features of urea cycle disorders?

Answer 7

Vomiting without diarrhoea 
Resp alkalosis 
Hyperammonaemia 
Neurological encephalopathy 
Avoidance/Change in diet (e,g. avoiding protein, taking protein supplements)

Question 8

What defects cause hyperammonaemia with metabolic acidosis and high anion gap?

Answer 8

defects In leucine, isoleucine, valine structures

ORGANIC ACIDURIAS

Question 9

What do organic acidurias present as in neonates?

Answer 9

Unusual odour of urine 
lethargy 
feeding problems 
truncal hypotonia / limb hypertonia 
myoclonic jerks
Cytopoenia

Question 10

What does Reye syndrome present as’

Answer 10

vomiting 
lethargy
increased confusion 
seizures 
decerebration 
respiratory arrest 

Encepalopathy + liver failure

Question 11

What is Reye Syndrojme triggered by?

Answer 11

aspirin
anti-emetics
valproate

Question 12

Who does Reye Syndrome occur in?

Answer 12

Children <14
Esp after chicken pox/flu
Triggered. by aspirin

Question 13

What metabolic presentation occurs with MCAD deficiency?

Answer 13

Hypoketotic hypoglycaemia

Question 14

What occurs in hypoglycaemic patients with MCAD?

Answer 14

They are unable to break down fatty acids , so they cannot make ketones even if they are hypoglycaemic

Question 15

What is the most common deficiency for galactosaemia?

Answer 15

Gal-1-PUT deficiency

Cannot break down carbohydrates

Question 16

How does galactosaemia present?

Answer 16

Liver disease: vomiting , hepatomegaly, conj hyperbilirubinaemia
hypoglycaemia
sepsis
diahrroez

Question 17

What becomes raised in Gal-1-PUT deficiency

Answer 17

Gal-1-P

Question 18

What does Gal-1-P excess cause?

Answer 18

Liver, kidney disease
bilateral cataracts (due to aldolase buildup)

Question 19

how do you treat galactosaemia?

Answer 19

Avoid galactose (milk)

Question 20

What is von Gierke’s disease?

Answer 20

Glycogen storage disease Type 1

inability to break down glycogen

Question 21

What glycemic state are people with Von Gierke’s?

Answer 21

HYPOgycaemic
+ lactic acidosis

because they can’t tap into their glycogen reserves in liver and skeletal muscle

Question 22

What is a mitochondrial disorder that occurs at birth?

Answer 22

Barth - cardiomyopathy, neutropenia, myopathyu

Question 23

What is a mitochondrial disorder that occurs t 5-15 yo?

Answer 23

MELAS

Question 24

What does MELAS present as?

Answer 24

Mitochondrial Encephalopahty
Lactic Acid
Strokes

Question 25

What is a mitochondrial disorder occurring at 12-30 yo?

Answer 25

Kearns- Sayre

Chronic progressive opthalmoplegia
retinopathy
deafness
ataxia

Question 26

What is lactate like in metabolic disorders?

Answer 26

HIGH

Question 27

What o cc urs to ATP and thereby to tissues in metabolic disorder?

Answer 27

Defective ATP production

Causes multisystem disease esp affecting organs with high energy requirement