Inborn error Weisfeld Flashcards
PKU
- Mode of inheritance?
- Due to?
autosomal recessive
PAH deficiency
- Phenylalanine hydroxylase
- Phenylalanine cannot be converted to tyrosine (precursor for niacin)
Assay to screen for PKU
Guthrie bacterial inhibition assay
- 3mm blood spots (+) if bacterial halo is seen (indicating high PA [ ])
Disease phenotypes can result from:
- Accumulation of metabolite A
- precursor toxicity - Overflow to products E or F
- alternative, potentially toxic metabolites - Reduced formation of metabolite D
- product deficiency - COmbo of all of the above
Severe levels of Phe
Moderate
Mild/benign
severe: >1200
moderate: 600-1200
mild/benign:
Maternal PKU presentation
Malformation in infants of mothers with poorly controlled PKU
- microcephaly
- low birth weight
- mental retardation
Long term management of PKU
Treatment for life
- Restrict PKU, but DO NOT eliminate it
- Provide adequate calories, protein, vit, minerals
- Maintain nl growth and development
Key management of Inborn Errors of Metabolism (IEM):
- Coma/encephalopathy
- remove offending agent
- NPO
- Stop catabolism
- dialysis
Name disease: Newborn Breast fed female Poor feeding, progressive lethargy Mild hypoglycemia Mild met acidosis Ketonuria
- what test can verify your guess
MSUD
- Ketones are not usually detected in newborns
- DNPH test should be pos
4 subunits can be affected in MSUD
E1 a
E1 b
E2
E3
These lead to a branched chain ketoacid dehydrogenase (BCKD) deficiency
Mode of inheritance of MSUD
Auto recessive
Deficiency in BCKD
Severe neonatal
Acute intermittent
Subacute chronic
presentations of MSUD
Severe neonatal
- few abnormalities on routine lab tests
- Maple syrup odor in urine
Acute intermit:
- late onset
- ataxia
- Ketoacidotic coma
- AA and ketoacid can be nl btwn attacks
Subacute chronic
- hypotonia and developmental delay
- failure to thrive
- spastic paraplegia
ACUTE tx of MSUD
- Eliminate dietary protein intake
- Supplement valine and isoleucine
- Provide adequate non-protein E source and aa that are NOT BCAA
- Avoid hypotonic fluids
- Treat cerebral edema
CHRONIC tx of MSUD
- Protein restricted diet supplemented with BCAA free medical foods
(MSUD coolers) - Leucine intake 400-600 in severe neonatal
600-800 after adolescence - Supplement valine and isoleucine
- Thiamine supplementation in some cases of E2 subunit def.
Tyrosinemia Type I
- cause
- What builds u?
FAH deficiency (downstream of Tyrosine)
- Tyr –> FAA cannot ultimately be broken into fumarate and acetoacetate
- Succinylacetoacetate forms due to alt path
Tyrosinemia Type 1 presentation
Early infancy
Late infancy
Any age
Early infancy (1-6 mo) - Liver disease (hepatic failure, cholestatic jaundice or cirrhosis with renal tubulopathy)
Late infancy:
- Rickets due to renal tubulopathy (Fanconi syndrome) with no liver failure
(leaky kidneys)
Any age
- Porphyria like attack
Tx of Tyrosinemia type 1:
- NTBC
- inhibits point in Tyrosine catabolic pathway
- -> Increases plasma Tyr
- -> Decreases production of FAA and succinylacetone - Phe and Tyr restriction (thanx to step 1)
- Liver transplant if hepatocellular carinoma develops
If pts with Tyrosinemia adhere to their NTBE drug tx, but not their Phe and Tyr restriction, what can result?
Plantar keratosis
- groadie yellow scaling on palms and soles
Classical untreated Homocystinuria sx
- skeletal malformations
- marfanoid habitus
- osteoporosis
- scoliosis - Recurrent thromboembolism
- Eye abnormalities
- developmental disability and neuropsychiatric sx
* most common in B6 non responsive forms
Classical Homocystinuria
- cause
- mode of inheritance
CBS deficiency (Cystathionine B- Synthase)
-all of these are Auto recessive!
Homocystinuria tx
- Pyridoxine (B6) if pt has responsive form
- Restrict dietary protein
- Methionine free food Supplement
- Oral Betaine
When should valproate therapy be avoided?
If pt has elevated ammonia levels
Most common urea cycle disorder
- x linked
- characteristic presentation
OTC (ornithine transcarbamylase) deficiency
PLasma aa:
- Low citrulline
- eleveated glutamine >1200
Urine acids
- elevated orotic acid
Ammonia scavenging medications
- sodium phenylacetate
2. sodium benzoate
