Inborn Errors: Urea Cycle Defects Flashcards
1
Q
Old phenotype of PKU
A
- ID plateauing during the first year of life. Irreversible after this
- Blond
- Blue eyes
- Musty odor
2
Q
PKU
A
- Deficiency of PAH (Requires BH4 as cofactor)
- Removal of Phe allows it to diminish and halt further degradation of mental status (more normal mental status)
- Newborn screening of bacterial inhibition assay to screen for PKU (Guthrie)
3
Q
Which criteria are used to determine if newborn screening is warranted for disease?
A
Wilson-Junger Criteria
4
Q
How do you treat Krabbe Disease?
A
Umbilical-Cord Blood Transplant…. very high mortality
5
Q
Minimum mandatory screen
A
- Aminoacidopathies
- Organic acidemias
- Dx of carbohydrate metabolism
- FA oxidation disorders
- Urea cycle disorders
- Some non-metabolic disorders
6
Q
Maternal PKU
A
Leads to the following in the child:
- microcephaly
- cardiac lesion
- mental retardation
7
Q
Tyrosine is a precursor of
A
- Dopamine and L-DOPA
2. Melanin
8
Q
** Disease phenotypes may result from: ***
A
- accumulation of a metabolite (precursor toxicity)
- overflow to alternative products (potentially toxic)
- Reduced formation of desired metabolite (product deficiency)
- A combo of all of the above
9
Q
PKU incidence etc
A
- AR inheritance
- 1:16,000 live births in US
- Rare variants of biopterin synthesis or recycling are also seen
10
Q
Hyperphenylalaninemia
A
Severe: Plasma Phe > 1200 microM
Moderate: 600-1200
Mild:
11
Q
Long term therapy for PKU
A
- 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
Q
Metabolic encephalopathies - management
A
- Remove offending agent (NPO, STOP cataboism, dialysis)
- Clinical phenotypes depend upon enzyme activity - lots of variables
- Vitamins and nutrition
13
Q
Are ketones normal in newborns?
A
Nope!
14
Q
MSUD and plasma AA profile
A
- Massive Leu
- Elevated Val
- Elevated Ile
- DNPH test
15
Q
MSUD
A
- Defects in branched chain ketoacid dehydrogenase
- AR Inheritance; P.Y391N in E1alpha protein
- Penn amish and mennonite population