Inborn Errors: Urea Cycle Defects Flashcards Preview

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Flashcards in Inborn Errors: Urea Cycle Defects Deck (18):
1

Old phenotype of PKU

1. ID plateauing during the first year of life. Irreversible after this
2. Blond
3. Blue eyes
4. Musty odor

2

PKU

1. Deficiency of PAH (Requires BH4 as cofactor)
2. Removal of Phe allows it to diminish and halt further degradation of mental status (more normal mental status)
3. Newborn screening of bacterial inhibition assay to screen for PKU (Guthrie)

3

Which criteria are used to determine if newborn screening is warranted for disease?

Wilson-Junger Criteria

4

How do you treat Krabbe Disease?

Umbilical-Cord Blood Transplant.... very high mortality

5

Minimum mandatory screen

1. Aminoacidopathies
2. Organic acidemias
3. Dx of carbohydrate metabolism
4. FA oxidation disorders
5. Urea cycle disorders
6. Some non-metabolic disorders

6

Maternal PKU

Leads to the following in the child:
1. microcephaly
2. cardiac lesion
3. mental retardation

7

Tyrosine is a precursor of

1. Dopamine and L-DOPA
2. Melanin

8

**** Disease phenotypes may result from: *****

1. accumulation of a metabolite (precursor toxicity)
2. overflow to alternative products (potentially toxic)
3. Reduced formation of desired metabolite (product deficiency)
4. A combo of all of the above

9

PKU incidence etc

1. AR inheritance
2. 1:16,000 live births in US
3. Rare variants of biopterin synthesis or recycling are also seen

10

Hyperphenylalaninemia

Severe: Plasma Phe > 1200 microM
Moderate: 600-1200
Mild:

11

Long term therapy for PKU

- restrict Phe but not eliminate it
- provide adequate calories, protein, vit and minerals
- maintain normal growth and development
"Tx for life"

- new form of biopterin available
- LNAA to compete for Phe
- Liver cell transplant?

12

Metabolic encephalopathies - management

1. Remove offending agent (NPO, STOP cataboism, dialysis)
2. Clinical phenotypes depend upon enzyme activity - lots of variables
3. Vitamins and nutrition

13

Are ketones normal in newborns?

Nope!

14

MSUD and plasma AA profile

1. Massive Leu
2. Elevated Val
3. Elevated Ile
4. + DNPH test

15

MSUD

1. Defects in branched chain ketoacid dehydrogenase
2. AR Inheritance; P.Y391N in E1alpha protein
3. Penn amish and mennonite population

16

3 presentations of MSUD

1. Severe neonatal form
- few abnormalities on lab tests
- maple syrup odor in urine

2. Acute intermittent form
- late onset
- ataxia
- ketoacidotic coma with normal AA and keto acids between attacks

3. Subacute chronic form
- hypotonia and dev delay
- failure to thrive
- spastic paraplegia

17

Acute Tx of MSUD

1. Eliminate dietary protein intake
2. Supplement Val and Ile
3. Avoid hypotonic fluids
4. Treat cerebral edema

18

Chronic Tx of MSUD

- protein restricted diet
- Leucine intake about 400-600 mg then 600-800 after adolescence
- supplement Val and Ile
- Thiamine supplementation in E2 deficiency