Inborn Errors of Met- Organic Acid DO Flashcards
Screening of IEoM measures ___ levels or tandem __ to measure quantities of __ and ___ in blood
reduced Alpha glucosidase activity
Reduced Lysosomal hydrolase activity
Phenylalanine
Citrate (2)
Hexacosanoic acid
Leucine
Methionine
Galactose
dz and next step
specific enzyme, mass spec, AA, acylcarnitines
GSD T2, Pompe
serum alpha-glucosidase enzyme assay
Mucopolysaccharidosis T1 (hurler) Leuk LH assay, urine GAGs
classic PKU
plasma AA
argininosuccinic aciduria, citrullinemia type 1
plasma NH3/AA
X Linked Adrenoleukodystrophy
plasma VLCFA analysis
MSUD, plasma AA
Classic galactosemia
erythrocyte GALT activity
Tyrosine
Acyclcarnitine C3
C5
C8 (C6/10)
C14
C16-OH
dz, next step
Tyrosinemia Type 1
plasma AA
Methylmalonic/propionic acidemia
urine OA, plasma acylcarn
isovaleric acidemia
same
MCAD, same
VLCAD
plasma acylcarn
LCHAD
urine OA, plasma acylcarn
All AA disorders result from __ enzyme def preventing metabolism of __, leading to __
each AA has Different ___
MSUD- def of branched chain __
normally metabolizes L, I, V
these __
__ is most toxic to brain, resulting in ___
Infant presents w __ and __, __, poor __
if untx, H, C, D w/in hours
may have characteristic __ w urine/cerumen
Dx MSUD w elevated __
confirmed w plasma __ demonstrating elevated L, I, V, A
AR, specific AA, accumulation
toxicities
alpha ketoacid dehydro
Leucine, isoleucine, valine
accumulate
leucine
acute neuro sx
lethargy/irritability, seizure, poor feeding
hypertonicity, coma, death
odor of maple syrup
leucine
AA, leucine, isoleucine, valine, alloisoleucine
PKU- def in enzyme ___, which hydroxylates __ to __
__ accumulates and is __ to brain, causing ___
infant develops __ and global __ during infancy/childhood
affected adults consuming __ develop __, __/__ probs
Dx PKU- inc ___
confirmed w measuring plasma __, demonstrating inc __
phenylalanine hydroxylase, phenylalanine to tyrosine
phenylalanine, toxic, permanent brain injury
microcephaly, devo delay
phenylalanine, mood do, attention/cognitive
phenylalanine
AA, phenylalanine
Tyrosinemia
deficinecy of __ (FAH), responsible for __ of tyrosine
__ accumulates in __ and __, resulting in organ damage
Fumarylacetoacetate broken down to __, detected in __
infant presents w __, __ from progressive LD
Kidney toxicity as __ w __ and __ (from phos loss in RT)
can lead to __ and ___
Dx w inc __
confirm w plasma __ w inc __, and __ in urine
famarylacetoacetate hydrolase, intermediate met
FAH, liver/kidney
succynlacetone, urine
FtT, hepatomegaly
RT dysfxn, RTA, hypophos
rapid deterioration/death
tyrosine
AA, tyrosine, succinylacetone
Homocystinuria
defective __ met leads to accumulation of __ and __
MCC is def of __ (CBS), preventing conversion of __ to ___
may result from IE of __ (VB12) synth, necessary for ___
CM- sx are ___
infants __ at birth, then get __ and mild __ in 1st yr
after 3, bcome __, __ and __ and ___
Dx- inc __, confirm w plasma __, w elevated __/__/__ and dec __
methionine, homocysteine/homocystine
cystathione B synthase, homocysteine to cystathione
cobalamin, methionine synthase
variable
normal, FtT, developmental delay
tall, arachnodactyly, ectopia lentis, TE events
methionine, AA
methionine, homocysteine/homocystine
cystathione
Urea cycle metabolizes __ from deamination of ___
Most Inheritance ___
Exception is __ def, which is __ (assc w __ &__ def)
Infants present w __, __, __ and __
as __ worsens, __ develops, resulting in __/_
most severe defects in __ def
boys w parial enzyme def may develop __ and mild elevations of __
Dx with inc __, suggesting __ (ASS def)
or ___ acidura (AS def)
others w inc __, confirm w plasma__ and urine __
ammonia, AA
AR
Ornithine transcarbamylase, XL
partial/complete
AMS, lethargy, poor feeding, vomiting
hyperammonemia, cerebral edema, coma/death
complete OTC def
mild sx, ammonia
citrulline, citrullinemia
argininosuccinic
ammonia, AA, orotic acid
OTC def
ASS def (Citrullinemia)
ASL def (argininosuccinic aciduria)
Arginine
Citrulline
Argininosuccinic Acid
Urine Orotic acid
Dec, dec, dec, inc
dec, inc, dec, inc
dec, inc, inc, inc
OA disorders
AA breakdown req __ to degrade protein byprodcts
enzymes responsible for __ breakdown also essential for __ degredation
elevation of plasma __ acylcarnitines also occurs
__ defects in degredation enzymes result in accumulation of __ in blood
Infant presents __, __ and __
progress to __, and __/__
lab shows __, w high __ and __
may have inc __/__ or __
odor of __ may be assc w __
several enzymes
OA, short chain FA
short odd chain
AR, OA
lethargy, vomiting, FtT
hypotonia, seizure/coma
Met acid, AGAP, ketosis
lactate, hyperammonemia, hypoGly
sweaty feet, isovaleric acidemia
Dx of OA disorders
detect inc ___ (MA/PA) or __ (IA)
confirm w measuring urine __ and plasma __
Methylmalonic acidemia
Proprionic acidemia
Isovaleric acidemia
Enzyme def, urine OA, plasma acylcarnitines
C3 acylcarnitine, C5 acyl
OA, acylcarnitines
methylmalonyl CoA mutase
MA/PA, inc C3
Propionyl CoA carboxylase, PA, inc C3
isovaleryl CoA Dehydro, I3HIA, inc C5
