Inborn Errors: Amino Acidopathies

Question 1

Liver Failure

Answer 1

Inborn errors:

- fructosemia, galactosemia, alpha-1-antitrypsin, tyrosinemia type 1, hemochoromatosis

Question 2

Elevated tyrosine and methionine; abundance of succinylacetone and delta-aminolevulinic acid

Answer 2

Tyrosinemia Type 1

Deficiency of fumarylacetoacetate hydrolase deficiency

• Common in Finland
• AR

Question 3

3 presenting forms of tyrosinemia type 1

Answer 3

1. Early in infancy - liver disease
2. Late infancy - Rickets due to renal tubulopathy with no obvious liver failure
3. Porphyria-like attack at any age

Question 4

Succinylacetone ___ delta aminolevulinic acid dehydratase activity

Answer 4

inhibits

causes porphyria like abdominal pain crises and peripheral neuropathy

Question 5

alpha fetoprotein

Answer 5

• unreliable as a marker in neonates

- otherwise marker of liver regen

Question 6

Tx of Tyrosinemia type 1

Answer 6

1. 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexane-dione (NTBC)
   - Inhibits 4-hydroxyphenylpyruvic acid dioxygenase, increases plasma tyrosine, decreased production of FAA and succinylacetone
2. Phe and Tyr restriction
3. Liver transplant if hepatocellular carcinoma develops

Question 7

Palmoplantar keratosis

Answer 7

Tyrosinemia Type 1

Question 8

Alkaptonuria

Answer 8

1. Black urine
2. Black pigmentation of cartilage and collagen
3. Degenerative arthritis from 4th decade

Question 9

Hypermethioninemia

Answer 9

1. deficiency of CBS
2. Accumulation of homocysteine and an elevation in methionine

Methionine is a 2ndary marker

Question 10

Diagnostic eval of hypermethioninemia

Answer 10

1. Labs:
   - elevated methionine, elevated homocystine, urine homocystine, urine organic acids normal, cyanide-nitroprusside test positive
2. Marfan like skeletal malformations, osteoporosis, scoliosis, most common in B6 non-responsive forms

Risk for recurrent VTE and premature atherosclerotic disease, eye abnormalities

Question 11

Classical homocystinuria

Answer 11

• AR inheritance
• 1/200,000
• Often missed on newborn screens
• 50% are B6 responsive (do a B6 challenge)

Question 12

Tx of homocystinuria

Answer 12

1. Restrict dietary protein
2. supplemented with methionine free medical foods
3. Oral betaine
4. Consider supplementation with B12, folate, and/or cysteine

Can give B6 if it is responsive

Question 13

Is ammonia only elevated in UCD?

Answer 13

No, also secondarily elevated in other inborn errors of metabolism

Avoid valproate in these pts at all costs!

Question 14

Triggers of hyperammonemia

Answer 14

• infection
• fever
• vomiting
• GI or other bleeding
• decreased energy or protein intake (fasting)
• Chemo
• catabolism
• exercise
• Drugs

Question 15

OTC deficiency

Answer 15

1. Most common disorder
2. X-linked disorder
3. Males first 2-3 days of life and usually fatal.
4. Females get a range based upon pattern of X-inactivation

Don’t forget to explore FHx!

Question 16

OTC blood gas

Answer 16

Respiratory alkalosis
Plasma ammonia elevated
Tachypneic

Question 17

OTC metabolites

Answer 17

1. Low citrulline
2. High glutamine
3. Elevated orotic acid

Question 18

Ammonia Scavenging Agents

Answer 18

1. Sodium phenylacetate

2. Sodium Benzoate

Question 19

UCD Tx strategies

Answer 19

• Dietary protein restriction
• ammonia scavenging meds
• L-arg or L-citrulline supplementation
• Hemodialysis or intravenous scavengers
• Consider liver transplantations