Urea Cycle Disorder

Question 1

2 major functions of urea cycle

Answer 1

1. Removal of nitrogenous waste

2. Synthesis of amino acids

Question 2

Primary location of urea cycle

Answer 2

Hepatocytes

Question 3

Consequences of acute elevation of ammonia

Answer 3

Seizures, coma, death

Question 4

Consequences of mild chronic elevations of ammonia

Answer 4

Brain atrophy, cognitive impairment

Question 5

Non genetics causes of hyperammonemia

Answer 5

Infections
Toxins
Trauma
Ischemia

Question 6

OTC inheritance and gene

Answer 6

XLR, OTC

Question 7

OTC enzyme deficiency

Answer 7

Ornithine transcarbamylase deficiency

Question 8

Plasma AA in OTC

Answer 8

Elevated: orotic acid and ammonia
Low: citrullinr, ASS, ARG

Question 9

ASS1 deficiency inheritance and gene

Answer 9

AR, ASS1

Question 10

ASS1 enzyme deficiency

Answer 10

Argininosuccinic acid synthase I deficiency

Question 11

Plasma AA profile for ASS1

Answer 11

Elevated: citrulline, glutamine, alanine, orotic acid
Low: ASA, Arg, ornithind

Question 12

ASL deficiency inheritance and gene

Answer 12

AR, ASL

Question 13

ASL enzyme deficiency

Answer 13

Argininosuccinate lyase deficiency

Question 14

Plasma AA profile for ASL

Answer 14

Elevated: ASA, citrulline, glutamine, ala
Low: arg, ornithind

Question 15

ARG deficiency inheritance and gene

Answer 15

AR, ARG1

Question 16

ARG enzyme deficiency

Answer 16

Arginase deficiency

Question 17

Plasma AA for ARG deficiency

Answer 17

Elevated: arginine

Question 18

NAGS and CPS1 deficiency inheritance and gene

Answer 18

AR, NAGS/CPS1

Question 19

NAGS and CPS1 enzyme deficiency

Answer 19

N-acetylglutsmate synthase

Carbomohl phosphate synthetase deficiency

Question 20

Plasma AA profile in NAGS/CPS1 deficiency

Answer 20

Elevated: glutamine, alanine
Low: citrulline, AAS, Arg, orotic acid

Question 21

Untreated OTC 2-3 days old

Answer 21

Progressive hyperammonemia encephalopathy

Question 22

Untreated OTC 1 week old

Answer 22

Lethal hyperammonemic encephalopathy

Question 23

Prenatal dx of OTC deficiency

Answer 23

Molecular testing of familial mutation

Question 24

Untreated ASS1 4-7 days old

Answer 24

Progressive hyperammonemia encephalopathy

Question 25

Untreated ASS1 1-2 weeks old

Answer 25

Lethal hyperammonemic encephalopathy

Question 26

Prenatal dx of ASS1

Answer 26

Molecular testing of familial mutation

ASS1 enzyme activity measured on CVS/amnio

Question 27

Untreated ASL deficiency 4-7 days old

Answer 27

Progressive hyperammonemic encephalopathy

Question 28

Untreated ASL deficiency 1-2 weeks old

Answer 28

Lethal hyperamonemic encephalopathy

Question 29

Progressive hyperammonemic encephalopathy

Answer 29

Poor feeding
Vomiting
Lethargy
Hyperventilation
Seizures

Question 30

Lethal hyperammonemic encephalopathy

Answer 30

Cerebral adema
Hypothermia
Coma
Respiratory failure
Death

Question 31

Prenatal dx of ASL deficiency

Answer 31

Molecular testing of familial mutation
ASL enzyme activity of CVS or amnio
Elevated arginosuccinic acid levels in amniotic fluid suggestive of ASL deficiency

Question 32

ARG deficiency after 1-3 years

Answer 32

Growth slows
Motor and cognitive development slows + regression
Spasticity and seizures develop

Question 33

Untreated ARG deficiency in adulthood

Answer 33

Severe MR, microcephaly
Short stature
Severe spasticity and joint contractures
Lack of ambulation, bowel and bladder control

Question 34

Prenatal dx for ARG deficiency

Answer 34

Molecular testing of familial mutation

ARG enzyme activity on RBCs (PUBs)

Question 35

Untreated NAGS and CPS1 deficiency

Answer 35

Neonatal hyperammonemia encephalopathy

Question 36

Prenatal dx of NAGS and CPS1

Answer 36

Molecular testing if familial mutation known