Inborn errors Flashcards
what are inborn errors of metabolism
disorders from enzyme defects in biochemical pathways that affect fat, protein, and carb metabolism or impaired organelle functioning
T or F: inborn errors are individually rare but collectively common
true
what type of mutations are inborn errors
autosomal recessive
what do we use for fuel in the body?
carbs/sugars-fats- proteins
first source of nrg in an emergency?
sugar
what is dextrose?
type of sugar
what type of disorder is PKU?
disorder of amino acid metabolism
what enzyme do ppl with PKU lack?
phenyalanine hydroxylase
what type of inheritance pattern is in PKU
autosomal recessive
what type of build up is there in PKU
build up of phenylanaline because they cannot convert phenylalanine to tyrosine
first disorder screened for at birth?
PKU
clinical features of PKU?
musty/mousy odor, light facial features, eczema, microcephaly, seizures
what occurs early on in PKU
intellectual disability
what occurs later on in PKU
psychiactric/behavioral probs
trmt for PKU?
low protein diet, PKU formula, drugs
what is an insidious disease?
one that builds up over time
what is tyrosine needed for?
melanin production
ex of insidious disease?
PKU
what is galactosemia a disorder of
carb metabolism
what type of inheritance pattern is galactosemia
autosomal recessive
what enzyme is deficient in galactosemia
galactose 1 phosphate uridyltransferase
early presentation of galactosemia
feeding difficulty, failure to thrive, hepatomegaly, liver damage, sepsis
later presentation/chronic complications of galactosemia
speech delays, cataracts, ataxia, dec IQ, failure to thrive
trmt for galactosemia?
galactose/lactose restriction; cannot have breast or cows milk
what type of disorder is maple syrup urine disease (MSUD)
organic acidemia
what type of inheritance pattern is MSUD
autosomal recessive
what enzyme is deficient in MSUD
branched chain ketoacid dehydrogenase
what are the BCAA
leucine, isoleucine, and valine
clinical symptoms of MSUD 2-3 days after birth ?
irritability, dec. responsiveness, poor PO intake
what population is MSUD common in
mennonite
how does MSUD progress over time
asymptomatic at birth and progresses over the next 7 days
when do BCAA build up in MSUD
as early as 12 hours
when are ketones present in urine in MSUD
2-3 days after birth
clinical symptoms of MSUD 4-6 days after birth ?
encephalopathy, vomiting, posturing, lethargy, apnea, abnormal mvmts
when is there noticible maple syrup/sweet odor in someones urine with MSUD
4-6 days after birth
clinical symptoms of MSUD 7+ days after birth ?
cerebral edema, respiratory failure, coma, death
chronic complications of MSUD
developmental delay, failure to thrive, inc risk of neuropsychiatric diseases (like depression, anxiety, ADHD)
trmt for MSUD?
chronic: restrict BCAA (especially leucine) and liver transplant
acute: stop catabolic state
name some glycogen storage disorders
von gierke, pompe, cori, anderson, McArdle, Hers, Tauris
what type of inheritance pattern do ppl with glycogen storage disorders usually have
autosomal recessive
what is there an issue with in ppl with glycogen storage disorders
glycogen synthesis or breakdown
what type of metabolic disorder is pompes disease
glycogen storage type 2
what is glycogen
sugar reserve
name some variable features of glycogen storage disorders
hypoglycemia, hepatomegaly, hyperlipidemia, exercise intolerance, myopathy, cardiomyopathy, rhabdomyolysis, muscle cramping, growth delays, failure to thrive
what type of inheritance pattern is pompes disease
autosomal recessive
what enzyme is deficient in pompes disease
alpha glucosidase
what occurs in pompes
glycogen cant be broken down so it builds up in lysosomes of skeletal muscle, heart, and liver
clinical features of pompes in infants
hypertrophic cardiomyopathy, hypotonia, muscle weakness, failure to thrive, respiratory infections, normal cognition, death by 2 y/o
clinical features of pompes late onset
progressive proximal muscle weakness, exercise intolerance, hepatomegaly, NO hypoglycemia
trmt for pompes
enzyme replacement
what disorder are ppl not able to rise from a chair
pompes (bc they dont have proximal muscle strength)
what type of inheritance pattern is von gierke disease
autosomal recessive
what type of metabolic disorder is von gierke disease
glycogen storage type 1
what enzyme is deficient in von gierke disease
glucose 6 phosphatase
where is there a build up of glycogen in von gierke disease
liver and kidney
clinical features of von gierke disease
hepatomegaly, renomegaly, doll like face
long term complications of von gierke disease
short stature, delayed puberty, osteoporosis, HTN, cognitive delay, neutropenia, inc risk of autoimmune disease
what happens if someone with von gierke fasts for over 2-3 hours
hypoglycemia, lactic acidosis, hypoglycemic seizures
trmt for von gierke disease?
small and frequent feeds, avoid/limit sucrose and lactose, soy based formulas, corn starch
when is von gierke usually diagnosed
4 months bc thats when feeds are spaced out
how are fatty acids metabolized
2 carbons at a time
how are disorders of fatty acid oxidation named
based on lengths of carbon chain unable to be further oxidized
what is acetyl coA needed for
ketone production
what is MCAD
medium chain acetyl CoA dehydrogenase deficiency
what type of inheritance pattern is MCAD
autosomal recessive
what is the MC FAOD
MCAD
what is there a build up of in MCAD
medium chain fatty acids (C8)
clinical features of MCAD
hypoketotic hypoglycemia, mepatomegaly, delayed development, SIDS
what may hypoketoic hypoglycemia cause in MCAD
seizures, lethargy, and coma
why may you get delayed development in MCAD
can be due to multiple episodes of hypoglycemia
trmt for MCAD
frequent feeds, cornstarch, lower fat diet
why do we need the urea cycle
dispose of nitrogen wastes
where does nitrogen come from
proteins
what type of inheritance pattern are urea cycle defects
autosomal recessive; EXCEPT for OTC (ornithine transcarbamylase), that’s x linked
MC urea cycle defect?
OTC deficiency (ornithine transcarbamylase)
what is there a build up of in urea cycle defects
ammonia
in urea cycle defects, who usually has higher ammonia levels
newborns
what is a marker of hyperammonemia
glutamine
what can occur acutely in urea cycle defects
hyperammonemia (VERY high levels), encephalopathy, respiratory alkalosis, lethargy, sepsis, vomiting, difficulty feeding, hypothermia
what may encephalopathy appear like in urea cycle defects
cerebral edema and mimic sepsis with bulging fontanelle
what can occur chronically in urea cycle defects
developmental delays
trmt for urea cycle defects?
limit protein intake, supplement with arginine and citrulline
what are nitrogen scavengers
sodium benzoate and sodium phenylbutyrate
what is there a build up of in lysosomal storage disorders
unprocessed materials SLOWLY over time in the lysosome
are the symptoms/features of lysosomal storage disorders there at birth or progressive
progressive; kids are normal at birth
how are lysosomal storage disorders classified?
based on the type of molecule that builds up
2 types of lysosomal storage disorders?
lipid disorders and mucopolysaccharide disorders
what type of disorder is tay sachs disease
lysosomal storage disorder: lipid disorder (ganglioside 2)
what type of mutation is in tay sachs and what is the inheritance pattern
autosomal recessive mutation in HEXA
what enzyme are ppl with tay sachs deficient in
hexosaminidase A enzyme (HEXA)
what population is tay sachs most common in
ashkenazi jews
what do you get an accumulation of in tay sachs
ganglioside 2 (GM 2)
clinical presentation of tay sachs birth-6 months
progressive motor weakness, myoclonic jerks, exaggerated startle response
clinical presentation of tay sachs 6-10 months
cherry red macula, regression, dec. vision
clinical presentation of tay sachs 10+ months
dec. mvmt and responsiveness, seizures, deterioration
when do ppl with tay sachs usually die by
4 years old
what type of inheritance is gauchers disease
autosomal recessive
what enzyme is deficient in gauchers
glucerebrosidase
what population is gauchers MC in
ashkenazi jews
clinical features of gauchers
hepatosplenomegaly, anemia, thrombocytopenia, leukopenia, bone disease, bone crises, pseudo-osteomyelitis
what are the two types of gauchers disease
neurological and non neurological involvement
what is mucopolysaccharidoses (MPS) 1 called
hurler syndrome
what inheritance pattern is MSP 1/hurler?
autosomal recessive
what is mucopolysaccharidoses (MPS) 2 called
hunter syndrome
what inheritance pattern is MSP 2/hunter?
x linked recessive
what MSP syndrome is there corneal clouding
MSP 1/hurler
clinical features of MSP disorders
coarse facial features, umbilical hernia, growth delay, intellectual disability, dysostosis multiplex (bony abnormalities), hepatosplenomegaly, valvular disease, cardiomyopathy, intellectual disability, protuberant abdomen
trmt for MSP disorders
enzyme replacement therapy, bone marrow transplant
what type of disorder is Lesch-Nyhan
disorder of purine (A-G) metabolism
what type of inheritance pattern is Lesch Nyhan
x linked recessive
what enzyme is there a deficiency in lesch nyhan
HGPRT 1
is Lesch-Nyhan an inborn error of metabolism
no
clinical features of les nyhan syndrome
motor disturbances, abnormal mvmts, cognitive impairments, behavioral abnormalities, injurious self behavior (head banging and biting fingers), macrocytic anemia, seizures, hyperuricemia
clinical symptoms of hyperuricemia
gout, orange crystals in diaper, kidney stones
who is MPS more common in: boys or girls
boys
do the symptoms for MPS come on acutely or are they progressive?
progressive: happen SLOW over time
is Lesch-Nyhan more common in boys or girls
boys bc its x linked
what is MTHFR
a gene commercially marketed to cause a variety of different disease processes including CV disease, cancer, preganancy loss, and thrombosis
what does MTHFR stand for and what is it involved in
methylenetetrafolate reductase which is involved in folate metabolism
