Protein Metabolism Disorders

Question 1

This category includes three types of problems

Answer 1

Amino acid disorders, organic acidemia, urea cycle defects

Question 2

Urea cycle defects

Answer 2

Transforms nitrogen into urea which can be excreted from body

6 possible enzyme deficiencies - most cause hyper-ammonia > 100-150 (except arginase def)

Question 3

Inheritance pattern of urea cycle defects

Answer 3

All are autosomal recessive except OTC which is x linked

Question 4

Symptoms of urea cycle defects

Answer 4

Median age of onset 2 years (50% present within 2 years but can also present in adolescence)

Term infant who’s well for 25-48 hours then deteriorate after feeding started bc can’t take protein load

Presenting sx are neurological (AMS, abnormal motor function, seizure) and GI (vomiting, poor feeding, diarrhea, nausea, constipation)

Question 5

Atypical presentation of urea cycle defect

Answer 5

Partial enzyme deficiency (partial OTC deficiency in female carriers)

Develop symptoms after increased protein intake or during periods of catabolic stress (trauma, surgery, pregnancy)

Protein aversion and prefers vegetarian diet bc protein gives them headache

Ammonia may only be abnormal during decompensation in patients with partial defects

Question 6

Arginase deficiency

Answer 6

Present in later infancy to preschool years. Spasticity, dystonia, ataxia. Does not cause hyperNH3

Question 7

Urea cycle defects

Answer 7

To differentiate among UCDs, obtain plasma amino acid and urine orotic acid

Question 8

Hyperammonia

Answer 8

Urea cycle defects have very high ammonia levels (can be 1000) in contrast to other etiologies with level rarely higher than 200-300s.

UCDs also have normal glucose, normal anion gap, and respiratory alkalosis (hyperventilation in response to cerebral edema)

Question 9

UCD management

Answer 9

Neuro injury correlates with duration of hyperNH3

Management

• rehydrate without overhydration
• remove nitrogen/ammonia using medication or dialysis
• stop protein intake and minimize catabolism (assisted respiration, treat sepsis)
• stimulate anabolism and uptake of nitrogen precursors by muscle

Question 10

UCD management

Answer 10

Don’t use steroid bc it increases protein catabolism

Valproic acid decreases urea cycle function and increases NH3 so shouldn’t be used to treat seizures