MIDTERM - METABOLIC DISORDERS Flashcards
Disruption of enzyme function can be
caused by failure to inherit the gene to produce a particular
enzyme, referred to as an ___.
inborn error of metabolism (IEM),
___is capable of screening the infant blood
sample for specific substances associated with particular
IEMs
MS/MS - tandem mass spectrophotometry
The most well known of the aminoacidurias,
Phenylketonuria
PKU is estimated
to occur in ____ of every 10,000 to 20,000 births
1
if undetected, results in severe mental retardation.
Phenylketonuria
. It was first identified
in Norway by Ivan Følling in 1934, when a mother with other
mentally retarded children reported a peculiar mousy odor to
her child’s urine
Phenylketonuria
PKU/ phenylketonuria is caused by failure to inherit the gene to produce the
enzyme ___.
phenylalanine hydroxylase
Urine testing using ___ may be used as a follow up test to ensure proper dietary control in previously diagnosed
cases and as a means of monitoring the dietary intake of pregnant women known to lack phenylalanine hydroxylase
ferric chloride
Urine tests for phenylpyruvic acid are based on the ferric chloride reaction performed by tube test. The addition of ferric chloride to urine containing phenylpyruvic acid produces a
permanent __ color
blue-green
The accumulation of excess tyrosine in the plasma is called
tyrosinemia
tyrosine metabolism may result from _- or __-
either inherited or metabolic defects.
because two reactions are directly involved
in the metabolism of tyrosine, the urine may contain excess tyrosine or its degradation products,
__- and ___.
p-hydroxyphenylpyruvic
acid and p-hydroxyphenyllactic acid
in tyrosyluria, Most frequently seen is a ___ in premature infants, which is caused by underdevelopment of the liver
function required to produce the enzymes necessary to complete the tyrosine metabolism
transitory tyrosinemia
type 1 tyrosenimia
is caused by the deficiency
of the enzyme __
fumarylacetoacetate hydrolase (FAH)
type of tyrosinemia that produces a generalized renal tubular disorder and progressive
liver failure in infants soon after birth. T
type 1 tyrosinemia
___tyrosinemia is
caused by lack of the enzyme tyrosine aminotransferase.
Type 2
a type of tyrosinemia which the Persons develop corneal erosion and lesions on the palms, fingers,
and soles of the feet believed to be caused by crystallization of
tyrosine in the cells
Type 2
Type 3 tyrosinemia is caused by lack of
the enzyme ___
p-hydroxyphenylpyruvic acid dioxygenase
This type of tyrosinemia can result in mental retardation if dietary restrictions of phenylalanine and tyrosine are not implemented.
type 3
second metabolic pathway also exists for
tyrosine. This pathway is responsible for the production of ___
melanin, thyroxine, epinephrine, protein, and tyrosine sulfate.
Deficient production of melanin
results in ___.
albinism
what are the normal byproducts of tyrosine on its secondary metabolic pathway?
melanin, thyroxine, epinephrine, protein, and tyrosine sulfate.
Increased urinary ___ darkens the urine. The darkening appears after the urine is exposed to air.
melanin
Elevated urinary
melanin is a serious finding that indicates proliferation of the
normal melanin-producing cells called
melanocytes
Elevated urinary
melanin is a serious finding that indicates proliferation of the
normal melanin-producing cells (melanocytes), producing a
malignant __.
melanoma
The name ___
was derived from the observation that urine from patients with
this condition darkened after becoming alkaline from standing
at room temperature.
alkaptonuria
This metabolic defect is actually
the third major defect in the phenylalanine-tyrosine pathway
and occurs from failure to inherit the gene to produce the
enzyme homogentisic acid oxidase
Alkaptonuria
alkaptonuria starts when the patient failed to inherit the gene to produce what enzyme?
homogentisic acid oxidase
This condition does not usually manifest itself clinically in early childhood, but observations of brown-stained or black-stained cloth diapers and reddish-stained disposable
diapers have been reported
Alkaptonuria
A high percentage of persons with alkaptonuria develop what other organ disorder?
liver and cardiac disorders.
homogentisic acid accumulates and deposited in the cartilage can cause ___
– disease under alkaptonuria
arthritis
The amino acids involved arfor maple syrup disease are
leucine, isoleucine, and valine.
maple syrup disease
\
The metabolic pathway for transamination of the three amino acids in the
liver to the keto acids (____).
alpha - ketoisovaleric,
alpha -ketoisocaproic,
and
alpha-keto-beta-methylvaleric
___ may be suspected when urine specimens, and sometimes even the patient, possess a characteristic
odor of “sweaty feet
Isovaleric acidemia
This odor is “sweaty feet”caused by the accumulation
of ___ due to a deficiency of enzyme ___ in the leucine pathway
isovalerylglycine; isovaleryl coenzyme A
The presence of isovaleric, propionic, and methylmalonic
acidemias can be detected by newborn screening programs
using ___.
MS/MS - tandem mass spectrophotometry
other acidemia aside from the isovaleric
Propionic and methylmalonic acidemias
Propionic and methylmalonic acidemias result from errors
in the metabolic pathway converting isoleucine, valine, threonine, and methionine to ___
succinyl coenzyme A.
___ is the immediate precursor to methylmalonic acid in this
pathway.
Propionic
acid
The major concern of the urinalysis laboratory in the metabolism of TRYPTOPHAN is the increased urinary excretion of the
metabolites ____ and ___
indican and 5-hydroxyindoleacetic acid (5-HIAA)
Early diagnosis of
Hartnup disease is sometimes made when a mother reports a
blue staining of her infant’s diapers, referred to as the “___.”
blue
diaper syndrome
The inherited defect in Hartnup disease affects not
only the intestinal reabsorption of tryptophan but also the
renal tubular reabsorption of other amino acids, resulting in
a generalized aminoaciduria (____).
Fanconi syndrome
a second metabolic pathway of
tryptophan is for the production of ___ used in the
stimulation of smooth muscles.
serotonin
Serotonin is produced from
tryptophan by the __ in the intestine and is carried through the body primarily by the platelets.
argentaffin cells
A noticeable odor of ___ may be present in the urine of people
with cystine metabolism disorders.
sulfur
____is marked by elevated amounts
of the amino acid cystine in the urine.
cystinuria
Regarded as a genuine IEM,
cystinosis
The presence of increased urinary cystine is not due to a defect in the metabolism
of cystine but, rather, to the ___
inability of the renal tubules to re-absorb cystine filtered by the glomerulus
The disorder cystinuria has two modes of inheritance
One in which reabsorption of all four amino acids—cystine, lysine, arginine, and
ornithine—is affected
and the other is
only cystine and lysine are not reabsorbed
Reduction of cystine by sodium
cyanide followed by the addition of nitroprusside produces
a __ color in a specimen that contains excess cystine
red-purple
Defects in the metabolism of the amino acid methionine produce an increase in ___ throughout the body.
homocystine
The increased __ can result in failure to thrive, cataracts,
mental retardation, thromboembolic problems, and death
homocystine
an additional screening test for homocystinuria must be per
formed by following a positive cyanide-nitroprusside test
result with a __ test, in which only homocystine will react
silver-nitroprusside test
function of silver nitrate to confirm the presence of homocystinuria
The use of silver nitrate in place of sodium
cyanide reduces homocystine to its nitroprusside-reactive
form but does not reduce cystine. C
__ are the intermediate compounds in the production
of heme
Porphyrins
three primary porphyrins
uroporphyrin, coproporphyrin, and protoporphyrin
porphyrin precursors
(a-aminolevulinic acid [ALA] and
porphobilinogen)
among the primary porphyrins, which one is not seen in urine?
protoporphyrin
The Centers for Disease Control and Pre
vention (CDC) recommends analysis of whole blood for the presence of __ as a screening test for lead poisoning.
free erythrocyte protoporphyrin (FEP)
Disorders of porphyrin metabolism are collectively termed
__.
porphyrias
An indication of the possible presence of ___
is the observation of a red or port wine color to the urine after
exposure to air.
porphyrinuria
The port wine urine color is more prevalent in
the ___, and staining of the teeth may
also occur
erythropoietic porphyrias
As seen with other inherited disorders, the presence
of ___ is sometimes suspected from a red discoloration of an infant’s diaper
congenital porphyria
The two screening tests for porphyrinuria use the __ and ___ under ultraviolet light in the 550- to 600-nm range.
Ehrlich reaction and fluorescence
test for porphyrinuria
The ___ can be used only for the detection of ALA and porphobilinogen.
Ehrlich reaction
__ must
be added to the specimen to convert the ALA to porphobilino
gen prior to performing the Ehrlich test.
Acetyl acetone
Testing for the presence of __is most useful
when patients exhibit symptoms of an acute attack.
porphobilinogen
Mucopolysaccharides is also called as
glycosaminoglycans
undigested Mucopolysaccharides are frequently found in the urine in a form of
dermatan sulfate, keratan sulfate, and heparan sulfate with the appearance of a particular substance being determined by the specific metabolic
error that was inherited
There are many types of mucopolysaccharidoses, but
the best known are
Hurler syndrome, Hunter syndrome, and
Sanfilippo syndrome
In both Hurler and Hunter syndromes,
the skeletal structure is ___ and there is severe ___;
abnormal; mental retardation
among the mucopolusaccharidoses which one is the only syndrome that has mental retardation is the only manifstation?
Sanfilippo syndrome
mucopolysaccharides accumulate in the cornea of the eye.
hurler syndrome
a mucopolysaccjaridoses that is inherited
as sex-linked recessive and is rarely seen in females
Hunter syndrome
___ and __ are the most promising treatments for mucopolysaccharidoses
Bone marrow transplants and gene replacement therapy
A disorder of purine metabolism known as ___
Lesch-Nyhan disease
a purine disorder that is inherited as a sex-linked recessive results in
massive excretion of urinary uric acid crystals.
Lesch-Nyhan
disease
In Lesh Nyhan disease,
Failure to inherit the gene to produce the enzyme _____ is responsible for the accumulation
of uric acid throughout the body.
hypoxanthine guanine
phosphoribosyltransferase
Patients suffer from severe
motor defects, mental retardation, a tendency toward self
destruction, gout, and renal calculi.
Lesch-Nyhan
disease
first sign is often
uric acid crystals resembling orange sand in diapers.
Lesch-Nyhan
disease
The presence of increased ____ is most
frequently due to an inherited disorder
urinary sugar (melituria)
The presence of increased urinary sugar (melituria) is most
frequently due to an inherited disorder. In fact, ____ was
one of Garrod’s original six IEMs.
pentosuria
Of primary concern is the presence of
___, indicating the inability to properly metabolize
galactose to glucose
galactosuria
Galactosuria can be caused by a deficiency in any of three
enzymes, ___, ___, and ___
galactose-1-phosphate uridyl transferase (GALT),
galactokinase, and UDP-galactose-4-epimerase.
Of these enzymes, it is ___ that causes the severe, possibly fatal
symptoms associated with galactosemia
GALT deficiency (galactose-1-phosphate uridyl transferase )
. a melituria that may be seen during pregnancy and lactation
Lactosuria
a melituria associated with parenteral feeding
Fructosuria
a melituria that is associated with ingestion of large amounts of fruit
pentosuria
