Inborn errors of metabolism Flashcards
G6PD deficiency has a higher incidence rate in individuals from ___, ___, ___, and ___
Africa
Asia
Mediterranean (Sardinian descent)
Middle East
G6PD follows ____ inheritance pattern
X linked recessive
results from mutations in the glucose 6 phosphate dehydrogenase enzyme
glucose 6 phosphate dehydrogenase deficiency
G6PD deficiency leads to the inability to form ____ and the accumulation of ____
NADPH
ROS
G6PD deficiency may lead to ____
hemolysis
_____ have high levels of vicine and convicine that are high in oxidative stressors therefore people with G6PD deficiency cannot eat these.
fava beans
G6PD deficiency impairs the ability of an erythrocyte to form ____ resulting in ____
NADPH
hemolysis
disease is due to a deficiency in methylmalonyl CoA mutase of adenosylcobalamin
methlymalonic acidemia
methylmalonic acidemia results in elevated levels of ____ (___) in the blood
methylmalonic acid
methylmalonate
methylmalonic acidemia leads to ___ and ____
metabolic acidosis
developmental problems
deficiency in branched chain a-keto acid dehydrogenase (BCKD)
maple syrup urine disease
in maple syrup urine disease levels of ____ and their ___ analogs are elevated in plasma and urine
branched chain a-amino acids
a-keto analogs
maple syrup urine disease leads to ____
neurologic problems (common)
maple syrup urine disease has a ___ mortality rate
high
treatment for maple syrup urine disease includes ___________
restricted dietary intake of the branched chain amino acids
classic form is due to a deficiency in cystathionine synthase
homocystinuria
homocystinuria results in an accumulation of ____ in the urine
homocysteine
homocystinuria leads to elevated levels of ___ and ___ in the blood but ___ is low
methionine
homocysteine
cysteine
homocystinuria results in ___, ____, ____, and ____
skeletal abnormalities
increased risk of clotting
lens dislocation
intellectual disability
most commonly encountered inborn error of metabolism
phenylketonuria
PKU follows ____ inheritance pattern
autosomal recessive
results from a homozygous or compound heterozygous mutations in the phenylalanine hydroxylase enzyme
PKU
PKU is clinically and biochemically characterized by _____
hyperphenylalanimia
PKU leads to levels of phenylalanine that are __ higher in plasma, urine and body tissues relative to normal
10 times
failure to treat PKU results in ____, ___, ___, and ___
intellectual disability
developmental delays
microcephaly
seizures
treatment of PKU includes _____ along with ____
restriction of phenylalanine
supplementation of tyrosine
treatment for PKU in essence, restricts the ___ for the enzymatic reaction and supplement with the ___ bypassing the necessity of the enzyme
substrate
product
maple syrup urine disease follows ___ inheritance pattern
autosomal recessive
converts phenylalanine to tyrosine
phenylalanine hydroxylase
enzyme that oxidatively decarboxylates the branched chain amino acids leucine, isoleucine and valine
BCKD
maple syrup urine disease results in a build up of the ____ forms of leucine, isoleucine and valine in the blood causing a toxic effects that interferes with ____
a-keto acid
brain function
maple syrup urine disease presents with ___, ___, ___, ___, ____ that may result in coma due to high levels of ___, ____ due to high levels of ___
feeding problems
vomiting
ketoacidosis
changes in muscle tone
neurologic problems
leucine
maple syrup smelling urine
isoleucine
homocystinuria follows ___ inheritance pattern
autosomal recessive
results from mutations in the enzyme csytathione B-synthase
homocystinuria
converts homocysteine to cystathionine
cystathione B-synthase
homocystinuria results in a build up of ___ and ___ levels in the blood and urine with low levels of _____ in plasma
homocysteine
methionine
cysteine
homocystinuria presents with ___, ____, ____, and ____
dislocation of the lens
skeletal abnormalities (long limbs and fingers)
intellectual disability
increased risk for developing thrombi
treatment for homocystinuria includes restriction of ___ and supplementation with ___ and ___
methionine
vitamin B12
folate
methylmalonic acidemia follows ___ inheritance pattern
autosomal recessive
results from mutations in the enzyme methylmalonyl CoA mutase
methylmalonic acidemia
converts methylmalonyl CoA into succinyl CoA which then enters the TCA cycle
methylmalonyl CoA mutase
methylmalonic acidemia results in the inability to metabolize the amino acids ___, ____, ___, and ___
valine
isoleucine
threonine
methionine
methylmalonic acidemia results in a build up of ____ (____) in the blood and urine
methylmalonic acid
methylmalonate
clinical presentation of methylmalonic acidemia is ___, ___, ___, ___, ___, ___, and ____
vomiting
dehydration
hypotonia
lethargy
hepatomegaly
feeding problems
metabolic acidosis
alkaptonuria follows ___ inheritance pattern
autosomal recessive
results from mutations in the enzyme homogenistic acid oxidase
alkaptonuria
converts homogentisate into maleylacetoacetate in the tyrosine degradation pathway
homogentistic acid oxidase
alkaptonuria results in the inability to metabolize ____
tyrosine
alkaptonuria results in a build up of ____
homogentisic acid
alkaptonuria presents with ____, ____, ____
homogentisic aciduria (urine contains elevated levels of HA)
early onset arthritis of the large joints
deposition of black pigment in the cartilage and collagenous tissue
alkaptonuria is not life threatening and usually presents ____ but may have ____
later in life
debilitating arthritis
albinism primarily follows ____ inheritance pattern
autosomal recessive
results from mutations in the copper requiring tyrosinase
type I albinism
catalyzes the first 2 steps in the synthesis of melanin from tyrosine
tyrosinase
albinism results in the inability to produce ____ thereby having an absence of ____
melanin
pigmentation in the skin, hair and eyes
general clinical presentation of urea cycle deficiencies that results because the amount of ammonia generation in the system surpasses the capacity of the urea cycle to remove the ammonia
hyperammonemia
hyperammonemia is a medical emergency because ammonia has ____
neurotoxic effects on CNS
two types of hyperammonemia
acquired
congenital
acquired hyperammonemia can result from ____
liver damage
most common urea cycle disorder
ornithine transcarbamylase deficiency
ornithine transcarbamylase deficiency follows ___ inheritance pattern
X-linked
results from mutations in the enzyme ornithine trascarbamylase
ornithine transcarbomylase deficiency
transfers a carbomoyl group from carbomoyl phosphate to ornithine to generate citrulline
ornithine trasncarbomylase
ornithine transcarbamylase deficiency results in the inability to ____
undergo early step in urea cycle
ornithine transcarbomylase deficiency presents with decrease in the levels of downstream products ___ and ___
citrulline
arginine
ornithine transcarbomylase deficiency in neonates presents with ___, ___, ___
lethargy
unwillingness to eat
poorly controlled breathing rate and body temperature
treatment for ornithine transcarbomylase deficiency may consist of ___ and taking ___ and ___ supplements
low protein diet
arginine
citrulline
arininosuccinate lyase deficiency follows ___ inheritance pattern
autosomal recessive
results from mutation in the enzyme argininosuccinate lyase
arginiosuccinate lyase deficiency (argininesuccinate aciduria)
removes fumerate from argininosuccinate to generate arginine and fumerate
argininosuccinate lyase
arininosuccinate lyase deficiency results in the inability to undergo ___ step in urea cylce
3rd
arginiosuccinate lyase deficiency presents with ___, ___, ___
lethargy
unwillingness to eat
poorly controlled breathing rate and body temperature
argininosuccinate lyase deficiency results in increased ___ and ___ in the urine with decreased levels of ____
argininosuccinate
citrulline
arginine
argininosuccinate lyase deficiency treatment may consists of ___ and taking ___ supplement
low protein diet
arginine
arginase I deficiency follows ___ inheritance pattern
autosomal recessive
results from mutation in the enzyme arginase I
arginase I deficiency (arginemia)
removes urea from arginine to produce ornithine which is then transported to the mitochondria and reenters the urea cycle
arginase I
arginemia results in the inability to undergo ___ step of the urea cycle
4th
arginemia results in build up of ___ and ___ in blood and urine
arginine
ammonia
arginemia may appear normal development from __-__ years but after presents with ____, ___, and ____
1
3
loss of developmental milestones
developmental delays
intellectual disability
treatment for arginemia consists of ___, ___ and ___ supplement
low protein diet
arginine restricted diet
essential amino acid
n-acetylglutamate synthase deficiency follows ___ inheritance pattern
autosomal recessive
results from mutation in the enzyme n-acetylglutamate synthase
n-acetylglutamate synthase deficiency
