Amino Acid Disorders Flashcards
PKU (cause/genetics)
deficiency of hepatic PAH (converts Phe to Tyr with BH4 cofactor)
AR
PKU (leads to …)
1) classic PKU (complete or near complete PAH defic)
2) Non-PKU HPU (hyperphenylalaninemia) Much less severe cognitive effects
3) Variant PKU
PKU: Phe levels should be …
… and why?
in Mom: 120-360 umol/L prior to conception and during preg
Phe is a TERATOGEN - elevated levels can cause birth defects
PKU pres/phenotypes
Rare to pres no as caught by newborn screen
Severe: >1200
Moderate: 600-1200
Mild/benign:
PKU: labs/diagnx
Newborn screen (24-72 hours after birth):
1) GUTHRIE CARD BIA
2) Flurometric analysis (fewer false positives)
3) Tandem mass spectormetry (more expensive but can diagnx many dz at once)
Looking for serum Phe >120 umol/L
PKU treat (classic)
Classic: RESTRICTED NATURAL PROTEIN diet for life (Phe-free formula)
PHE INTAKE 240-350 mg/day to maintain 120-360 mmol.L serum Phe
Adjuvant 6R-BH
PKU treat (non-PKU HPA, and women with PAH defic)
non-PKU HPA: treatment maybe not nec if Phe
MSUD (genetics)
And increased risk for?
AR, BCKAD defic (branched chain ketoacid dehydrogenase)
INCREASED RISK for ADHD, depression, anxiety
BCKDHA E1a: MSUD 1A
BCKDHB E1b: MSUD 1B
DBT (E2): MSUD 2
MSUD pres
Maple syrup odor in cerumen at 12-24 hrs
KETONURIA, irritiability, poor feeding
ENCEPHALOPATHY (lethargy, apnea, fencing and bicycling odd movements –>coma and resp failure (in 10 days)
MSUD diagnx
Elveated srum BCAA (leu, isoleu, val)
Ketonuria
Low BCKAD activity
MSUD treat
Eliminate dietary protein with judicious isoleu an val (400-600)
Poss dialysis to remove BCAA but insufficient
Liver transplant!!
Tyrosinemia (genetics and types)
AR, FAH defic (fumarylacetoacetate hydrolase)
Type 1: hepatorenal –> pitisinone
Type 2: oculocutaneous: tyr crystals in eyes, keratosis on palms and soles
Type 3: may be asymptomatic, some dev delay
Tyrosinemia (pres)
Can be:
1) 1-6 mos
2) Later in 1st year with liver and renal dysfxn WITH FAILURE TO GROW AND RICKETS
Type 2: risk of keratitis
Type 1: HEPATOCELLULAR CARCINMOA
If untreated: neuro crises then death before 10 yo
Tyrosinemia Diagnx (serum and urine)
Decreased FAH activity
Serum: high succinylacetone, Tyr, Met, Phe
Urine: high succinylacetine, Tyr metabolites, ALA
Tyrosinemia Treat
Nitisinone, NTBC (decreases succinylacetone), Phe and Tyr dietary restriction
Liver transplant if carcinoma
Homocysteinuria (genetics/phenotypes)
AR, variable expressivity
Defect in CBS enzyme (that converts homocysteine –> cystathionine)
2 phenotypes: B6 responsive (milder) and non-responsive
Homocysteinuria (pres)
Skeletal defects
Myopia or ectopio lentis
Recurrent thromboembolism (major cause of early death)
Dev disability and neuropsych symptoms
Homocysteinuria (diagnx/labs)
Elev methionine and homocysteine
Low CBS activity
Often MISSED on newborn screen
Homocysteinuria treat
B6 aka pyroxidine (if responsive)
Betaine, folate, B12 supplement
PROTEIN RESTRICTED DIET (serum HC
Cornerstone of tx
dietary therapy +/- pharmacologic doses of enzyme cofactors
Some amount of the a.a. is necessary for normal growth/development
AND remember: not all inborn errors and reliably detected on the newborn screen
