Metabolism Disorders - Exam 4 Flashcards
What do congenital metabolic disorders arise from? What type of inheritance are the majority? How are they dx?
the absence or abnormality of an enzyme or its cofactor, leading to either accumulation or deficiency of a specific metabolite
autosomal recessive
Diagnosis via enzyme essays or genetic testing
What are the three products of carbohydrate metabolism?
glucose
fructose
galactose
What are the two components of sucrose? Lactose?
Sucrose = Glucose + Fructose
Lactose = galactose + glucose
_____ found in fruit, vegetables, honey, high fructose corn syrup, sucrose, sorbitol
____ is broken down from starches, lactose, maltose and sucrose
Fructose
Glucose
______ functions as the long-term storage for excess glucose. What are the two places it is stored? When is it formed?
glycogen
liver and muscle cells
Formed during periods of dietary carbohydrate loading
____ is converted to glucose for energy throughout the body and CNS. What is it responsible for?
liver glycogen
glucose homeostasis in between meals and during periods of fasting
_____ is converted to glucose during periods of ?????
muscle glycogen
high energy muscle activity
When is glycogen broken down?
Broken down when glucose demand is high or dietary availability is low
____ Defects in glycogen metabolism results in an accumulation of glycogen in the tissues. What two organ systems will determine clinical presentation?
glycogen storage diseases
liver and muscles
hypoglycemia
+/- hepatomegaly
muscle pain
cramps
rhabdomyolysis
cardiomyopathy
conduction defects
delayed growth in children
progressive weakness involving trunk and extremities
myoglobinuria
What am I?
When do s/s usually appear?
What is the tx?
glycogen storage disease
Symptoms occur after short periods of moderate to intense exercise
Avoid hypoglycemia by eating frequent smaller meals
Enzyme replacement therapy may be available for some subtypes
Treatment of complications (ie rhabdomyolysis)
What does myoglobinuria present like in a pt with glycogen storage disease?
Myoglobinuria will present as blood (heme) in urine on a dipstick. When the microscopic eval is done no RBC’s will be seen.
What are common lab findings on a pt with glycogen storage dz?
Lab findings of hypoglycemia, elevated LFT’s and/or CPK
Genetic testing
What is CPK? When it is used?
Creatinine Phosphokinase (CPK) - an enzyme that is located in the muscles, heart and the brain. When cells are damaged in these organs CPK is released.
aka enzyme released from muscle cells as they break down aka signals that muscle cells are breaking down (not a good thing)
will be high in glycogen storage dz
How is fructosemia inherited? What are the 3 subtypes?
autosomal recessive: inability to metabolize fructose
fructokinase (Essential Fructosuria)
fructose 1,6-bisphosphate aldolase - aka aldolase B (Hereditary Fructose Intolerance)
fructose 1,6-diphosphatase (FDPase) (aka fructose 1,6-bisphosphatase)
Essential Fructosuria is _____
Hereditary Fructose Intolerance is _____
FDPase is _____
fructokinase
fructose 1,6-bisphosphate aldolase - aka aldolase B
fructose 1,6-diphosphatase
_____ is a benign (asymptomatic) condition resulting from a lack of fructokinase. **What is the pathophys behind it? What is the tx?
Essential fructosuria
Incomplete metabolism of fructose in the liver leading to its excretion in urine aka fructose and sucrose just gets peed out
nothing! does NOT cause problems
Hereditary fructose intolerance is an inadequate breakdown of fructose causing a _____ of fructose-1-phosphate in the ???? (3 organs). What does it lead to?
toxic accumulation
liver, kidney and small intestine
cell death
vomiting, jaundice, hepatomegaly
crying due to abdominal pain
symptoms of hypoglycemia (lethargy/irritability/convulsions)
failure-to-thrive
infant is initially healthy and asymptomatic
What am I?
When do s/s appear?
Hereditary Fructose Intolerance
Symptoms begin upon ingestion of fructose or sucrose: usually from fruit, sweetened cereal or sucrose containing formula
formula fed babies will show signs earlier but breast fed babies will be around 4-6 months when they first are introduced to baby food
How do you confirm dx of Hereditary Fructose Intolerance? What is the tx? What are 2 common complications?
genetic testing
complete avoidance of fructose and sucrose
liver and renal failure
Which type of fructosemia enzyme def is VITAL for gluconeogenesis? What is the result?
Fructose 1,6-bisphosphatase
deficiency of FDPase results in inadequate glucose production during periods of fasting (between meals and during sleep)
aka cannot produce glucose through gluconeogenesis due to lack of the enzyme
hypoglycemia
acidosis (due to lactate build up)
respiratory rate
nausea
vomiting
lethargy
What am I?
What is the tx?
Fructose 1,6-bisphosphatase Deficiency
avoid prolonged fasting
avoid fructose
**acidosis: body compensates by trying to blow off excess CO2 (acid) and respiratory rate will be elevated
What is galactosemia? How is it inherited?
autosomal recessive
lack of metabolism of galactose leading to a toxic accumulation of galactose-related molecules in various organs
Name 4 fruits/veggies that have galactose? What is the primary source?
tomatoes, brussels sprouts, bananas, and apple
human/cow milk and baby formula
What are the three different galactosemia enzyme deficiencies? What is the MC? What is the most severe?
**Galactose-1-phosphate uridyl transferase (GALT) deficiency (type 1- Classic galactosemia)
the most common and severe type
Galactokinase deficiency (GALK)(type 2)
Galactose epimerase deficiency (GALE)(type 3)
Normal at birth
decreased appetite
vomiting
diarrhea
hepatomegaly
jaundice
failure to thrive
cataract within 2 weeks
What am I?
What is the cataract formation due to?
Classic Galactosemia - GALT - Type 1
galactitol deposition
sepsis, intellectual deficits, movement disorders, ovarian failure (females), liver/kidney failure. Are all complications of ______
classic galactosemia
What is the major presenting difference between GALT and hereditary fructose intolerance?
Hereditary Fructose Intolerance will have hypoglycemia
GALT will have cataract formation
_____ type of galactosemia primarily presents with a cataract.
_____ ranges from asymptomatic to classic presentation
GALK
GALE: has a range of presenation
Is GALT enzyme def included in a newborn screening? What enzymes will be elevated? reduced?
YES!
RBC galactose-1-phosphate - elevated in GALT deficiency
GALT enzyme activity - reduced in GALT deficiency
What is the tx for GALT?
Minimize dietary galactose by
Discontinue breastfeeding or traditional formula
Use soy-based formulas (ie Alsoy, Isomil, ProSobee)
Later avoid dairy products; lactose-free may be safe later on
Galactose-1-phosphate uridyl transferase deficiency is ____
Uridine diphosphate galactose 4-epimerase def is _____
Galactokinase def is _____
GALT
(UDP) (GALE)
GALK
What are three main functions of AA? When does dysfunction occur? Are AA disorders included in the newborn screening?
building blocks for proteins and synthesis of hormones and neurotransmitters
Dysfunction occurs when the amino acids are unable to catabolize (break down) which results in an accumulation of the AA compound in the blood or urine aka cannot break down AA which leads to increased levels of AA in the serum
YES!
Phenylketonuria results in a deficiency of an enzyme called _____. How is it inherited? What is it responsible for?
phenylalanine hydroxylase (PAH)
autosomal recessive
PAH responsible for converting phenylalanine → tyrosine
What type of foods are high in phenylalanine? Low?
PKU leads to a toxic accumulation of phenylalanine in the _____. What happens next?
brain
Phenylalanine excess results in destruction of the myelin (fatty covering)of individual nerve fibers aka destroys myelin
What does the severity of PKU depend on? What is considered “classic PKU”? What ethnicity is MC?
amount of enzyme lost, ranges from mild - complete absence
classic = complete absence of enzyme
MC: in white and native american
normal at birth
loss of appetite
weakness
vomiting
irritability
Epilepsy
Abnormal gait/posture/stance
loss of executive functioning
decreased motor functioning
What am I?
What happens if left untreated? Why?
Phenylketonuria (PKU)
Blue eyes, light hair, and skin
Phenylalanine interferes with melanin production
How do you dx PKU?
newborn screening
Phenylalanine interferes with melanin production
What is the tx for PKU? What food do they need to avoid?
Dietary restriction of phenylalanine:
Avoid meats, dairy, nuts, aspartame
**supplement tyrosine
sapropterin
pegvaliase
______ activates PAH to promote the breakdown of phenylalanine. Can you rx to kids?
sapropterin (Kuvan)
_____ degrades phenylalanine. Can you rx to kids?
pegvaliase (Palynziq)
NO! adults only
Which of the two drugs that reduce blood phenylalanine must you have some enzyme present in order for it to work?
sapropterin (Kuvan) must have some enzyme present
**aka will not work in complete enzyme absence
______ A deficiency in the enzyme complex (branched-chain ketoacid dehydrogenase complex - [BCKDC]) required to break down branch-chain amino acids¹ (BCAA). How is it inherited?
Maple Syrup Urine dz
autosomal recessive
What is the function of BCAA (branch chain AA)? Name 3
stimulate the building of protein in muscle and possibly reduce muscle breakdown
leucine
isoleucine
valine
Def in branched-chain ketoacid dehydrogenase complex BCKDC] lead to ??? What is the result?
accumulation of these BCAA and their byproducts throughout the body
neuroinflammation
Elevation of plasma _____ causes maple syrup odor. Urine has a sweet odor, much like burnt caramel in ____. Name some common sources.
isoleucine
maple syrup urine dz
eggs, soy protein, white fish, pork, beef, tofu, parmesan, sesame
What is the MC form of maple syrup urine dz? How much enzyme activity? What is the form? enzyme activity?
Classic MSUD - < 3 percent enzyme activity
Non-classic MSUD - 3-30% enzyme activity
symptoms begins within 48 hours - 2 weeks
irritability
poor feeding
vomiting
lethargy
dystonia
apnea
seizures
cerebral edema, can die
What am I?
How is it dx?
classic MSUD
newborn screening
prenatal screening is available
onset is anytime during infancy or childhood
epigastric pain
vomiting
anorexia
muscle fatigue
hyperactivity
sleep disturbance
stupor
decreased cognitive function
dystonia
ataxia
s/s are exacerbated by physical stress
What am I?
What is the management for both types?
Non-classic MSUD
-strict protein restriction (medical grade formula/food)
-trial of thiamine supplementation for 4 weeks
-control metabolic decompensation by hemodialysis if needed
-liver transplant for classic MSUD because 10% enzyme is better than 0%
in maple syrup urine dz, you want to inhibit further protein catabolism and enhance protein synthesis by what 3 things?
Discontinue protein intake x 24-48 hours
IV glucose - provides calories (prevents protein catabolism for energy)
IV insulin if glucose is > 130 mg/dL
insulin enhances endogenous protein synthesis
homocystinuria is due to the dysfunction of the metabolism of the amino acid ____ results in an accumulation of _____ and diminished _____. What is the MC enzyme deficiency?
methionine
homocysteine
cysteine
cystathionine β-synthase
in homocystinuria, elevated ____ results in abnormal production of ____ and _____. What is there function?
homocysteine
elevated elastin and fibrillin
function: maintain the integrity of tissues such as blood vessels, lung, skin and ocular ligaments aka connective tissue and vasculature
What is the effect of homocysteine on the neurological system? What are the results?
excitatory effects on the neurologic system
results in cognitive developmental delays and seizures aka problems with motor development
What is a common ocular problem seen in pts with homocystinuria? Why does this happen?
lens dislocation
Low cysteine levels are thought to weaken the fibers holding the lens of the eye in place
