Urea Cycle Disorders

Question 1

Urea cycle purpose

Answer 1

Get nitrogen out of the body

Question 2

Final product of urea cycle

Answer 2

Make arginine that becomes urea

Question 3

Arginine supplementation does what?

Answer 3

Replaces low arginine levels
Stimulates NAGS reaction which stimulates CPS 1 (enzyme important for capturing ammonia)
Stimulates metabolites that flow into ornithine and cirtulline which keep the cycle going

Question 4

Urea is major disposal form of

Answer 4

Amino groups from proteins

Question 5

Urea is sole source of

Answer 5

Endogenous production of arginine

Question 6

Urea formation and excretion locations

Answer 6

Formation in liver…excretion in kidney

Question 7

Urea cycle disorder causes

Answer 7

Could be from cofactor…could be from enzyme defect

Question 8

Dysfunction of urea cycle results in

Answer 8

Neurologic changes because no other ways to clear ammonia

Question 9

Hyperammonemia type 1 defect

Answer 9

CPS 1 defect

Question 10

Hyperammonemia type 2 defect

Answer 10

Ornithine transcarbamoylase

Question 11

Citrullinemia defect

Answer 11

Argininosuccinate synthetase

Question 12

Argininosuccinic aciduria defect

Answer 12

Argininosuccinase

Question 13

Hyperarginemia defect

Answer 13

Arginase

Question 14

2 most severe types

Answer 14

CPS-1 and OTCase

Question 15

Main clinical manifestations of urea dzs

Answer 15

Most are neurologic

Question 16

Neurologic posturing

Answer 16

Clenached position not normal

Question 17

Eyes and urea cycle

Answer 17

Papilledema due to intercranial pressure

Question 18

Liver and urea cycle defect

Answer 18

Hepatomegaly

Question 19

Tx for urea cycle disorders

Answer 19

Decrease protein
Dialysis
Arginine chloride and nitrogen scavengers (IV)
Arginine become essential 
Liver transplant

Question 20

Benzoate

Answer 20

Converte to benzl CoA and then to hippurate…scavenges glycine

Question 21

Phenylacetate

Answer 21

Converted to phenylacetyl-CoA and then phenylacetylglutamine…scavenges glutamine (glutamine has 2 nitrogens)

Question 22

Glycine and glutamine good targets because

Answer 22

They are used fuel urea cycle…just need to get below toxic level

Question 23

Hyperammonemia type 1

Answer 23

CPS 1 defect
Rapid hyperammonemia during newborn period
Risk of hyperammonemia througout life

Question 24

Hyperammonemia type 2

Answer 24

OTC deficinecy
X-linked
Often deadly
Could be asymptomatic til adulthood and females that are heterozygous could have variety of symptoms

Question 25

Ctrullinemia type 1

Answer 25

Arginosuccinate synthase def
Autosomal rec
Lethargy with mental retardation
Hyperammonemia

Question 26

tx for citrullinemia

Answer 26

Restrict protein and emphasize other caloric sources
Use nitrogen scavengers
May need dialysis
Long term administer sodium phenylbutyrate and arginine
May need liver transplant

Question 27

Argininosuccinic aciduria

Answer 27

ASL deficiency
Rapid onset hyperammonemia
Past point in cycle where waste nitrogen incorportated into cycle
Only tx is arginine supplmentation
Trichorrhexias nodosa (response to arginine)
Hepatic enlargement and increased transaminases

Question 28

Hyperargininemia

Answer 28

ARG def
Not typically rapid onset hyperammonemia
Spasticity with tremor, ataxia and choreoathetosis
Growth affected