Inborn errors Flashcards
1
Q
what are inborn errors of metabolism
A
disorders from enzyme defects in biochemical pathways that affect fat, protein, and carb metabolism or impaired organelle functioning
2
Q
T or F: inborn errors are individually rare but collectively common
A
true
3
Q
what type of mutations are inborn errors
A
autosomal recessive
4
Q
what do we use for fuel in the body?
A
carbs/sugars-fats- proteins
5
Q
first source of nrg in an emergency?
A
sugar
6
Q
what is dextrose?
A
type of sugar
7
Q
what type of disorder is PKU?
A
disorder of amino acid metabolism
8
Q
what enzyme do ppl with PKU lack?
A
phenyalanine hydroxylase
9
Q
what type of inheritance pattern is in PKU
A
autosomal recessive
10
Q
what type of build up is there in PKU
A
build up of phenylanaline because they cannot convert phenylalanine to tyrosine
11
Q
first disorder screened for at birth?
A
PKU
12
Q
clinical features of PKU?
A
musty/mousy odor, light facial features, eczema, microcephaly, seizures
13
Q
what occurs early on in PKU
A
intellectual disability
14
Q
what occurs later on in PKU
A
psychiactric/behavioral probs
15
Q
trmt for PKU?
A
low protein diet, PKU formula, drugs
16
Q
what is an insidious disease?
A
one that builds up over time
17
Q
what is tyrosine needed for?
A
melanin production
18
Q
ex of insidious disease?
A
PKU
19
Q
what is galactosemia a disorder of
A
carb metabolism
20
Q
what type of inheritance pattern is galactosemia
A
autosomal recessive
21
Q
what enzyme is deficient in galactosemia
A
galactose 1 phosphate uridyltransferase
22
Q
early presentation of galactosemia
A
feeding difficulty, failure to thrive, hepatomegaly, liver damage, sepsis
23
Q
later presentation/chronic complications of galactosemia
A
speech delays, cataracts, ataxia, dec IQ, failure to thrive
24
Q
trmt for galactosemia?
A
galactose/lactose restriction; cannot have breast or cows milk
25
what type of disorder is maple syrup urine disease (MSUD)
organic acidemia
26
what type of inheritance pattern is MSUD
autosomal recessive
27
what enzyme is deficient in MSUD
branched chain ketoacid dehydrogenase
28
what are the BCAA
leucine, isoleucine, and valine
29
clinical symptoms of MSUD 2-3 days after birth ?
irritability, dec. responsiveness, poor PO intake
30
what population is MSUD common in
mennonite
31
how does MSUD progress over time
asymptomatic at birth and progresses over the next 7 days
32
when do BCAA build up in MSUD
as early as 12 hours
33
when are ketones present in urine in MSUD
2-3 days after birth
34
clinical symptoms of MSUD 4-6 days after birth ?
encephalopathy, vomiting, posturing, lethargy, apnea, abnormal mvmts
35
when is there noticible maple syrup/sweet odor in someones urine with MSUD
4-6 days after birth
36
clinical symptoms of MSUD 7+ days after birth ?
cerebral edema, respiratory failure, coma, death
37
chronic complications of MSUD
developmental delay, failure to thrive, inc risk of neuropsychiatric diseases (like depression, anxiety, ADHD)
38
trmt for MSUD?
chronic: restrict BCAA (especially leucine) and liver transplant
acute: stop catabolic state
39
name some glycogen storage disorders
von gierke, pompe, cori, anderson, McArdle, Hers, Tauris
40
what type of inheritance pattern do ppl with glycogen storage disorders usually have
autosomal recessive
41
what is there an issue with in ppl with glycogen storage disorders
glycogen synthesis or breakdown
42
what type of metabolic disorder is pompes disease
glycogen storage type 2
43
what is glycogen
sugar reserve
44
name some variable features of glycogen storage disorders
hypoglycemia, hepatomegaly, hyperlipidemia, exercise intolerance, myopathy, cardiomyopathy, rhabdomyolysis, muscle cramping, growth delays, failure to thrive
45
what type of inheritance pattern is pompes disease
autosomal recessive
46
what enzyme is deficient in pompes disease
alpha glucosidase
47
what occurs in pompes
glycogen cant be broken down so it builds up in lysosomes of skeletal muscle, heart, and liver
48
clinical features of pompes in infants
hypertrophic cardiomyopathy, hypotonia, muscle weakness, failure to thrive, respiratory infections, normal cognition, death by 2 y/o
49
clinical features of pompes late onset
progressive proximal muscle weakness, exercise intolerance, hepatomegaly, NO hypoglycemia
50
trmt for pompes
enzyme replacement
51
what disorder are ppl not able to rise from a chair
pompes (bc they dont have proximal muscle strength)
52
what type of inheritance pattern is von gierke disease
autosomal recessive
53
what type of metabolic disorder is von gierke disease
glycogen storage type 1
54
what enzyme is deficient in von gierke disease
glucose 6 phosphatase
55
where is there a build up of glycogen in von gierke disease
liver and kidney
56
clinical features of von gierke disease
hepatomegaly, renomegaly, doll like face
57
long term complications of von gierke disease
short stature, delayed puberty, osteoporosis, HTN, cognitive delay, neutropenia, inc risk of autoimmune disease
58
what happens if someone with von gierke fasts for over 2-3 hours
hypoglycemia, lactic acidosis, hypoglycemic seizures
59
trmt for von gierke disease?
small and frequent feeds, avoid/limit sucrose and lactose, soy based formulas, corn starch
60
when is von gierke usually diagnosed
4 months bc thats when feeds are spaced out
61
how are fatty acids metabolized
2 carbons at a time
62
how are disorders of fatty acid oxidation named
based on lengths of carbon chain unable to be further oxidized
63
what is acetyl coA needed for
ketone production
64
what is MCAD
medium chain acetyl CoA dehydrogenase deficiency
65
what type of inheritance pattern is MCAD
autosomal recessive
66
what is the MC FAOD
MCAD
67
what is there a build up of in MCAD
medium chain fatty acids (C8)
68
clinical features of MCAD
hypoketotic hypoglycemia, mepatomegaly, delayed development, SIDS
69
what may hypoketoic hypoglycemia cause in MCAD
seizures, lethargy, and coma
70
why may you get delayed development in MCAD
can be due to multiple episodes of hypoglycemia
71
trmt for MCAD
frequent feeds, cornstarch, lower fat diet
72
why do we need the urea cycle
dispose of nitrogen wastes
73
where does nitrogen come from
proteins
74
what type of inheritance pattern are urea cycle defects
autosomal recessive; EXCEPT for OTC (ornithine transcarbamylase), that's x linked
75
MC urea cycle defect?
OTC deficiency (ornithine transcarbamylase)
76
what is there a build up of in urea cycle defects
ammonia
77
in urea cycle defects, who usually has higher ammonia levels
newborns
78
what is a marker of hyperammonemia
glutamine
79
what can occur acutely in urea cycle defects
hyperammonemia (VERY high levels), encephalopathy, respiratory alkalosis, lethargy, sepsis, vomiting, difficulty feeding, hypothermia
80
what may encephalopathy appear like in urea cycle defects
cerebral edema and mimic sepsis with bulging fontanelle
81
what can occur chronically in urea cycle defects
developmental delays
82
trmt for urea cycle defects?
limit protein intake, supplement with arginine and citrulline
83
what are nitrogen scavengers
sodium benzoate and sodium phenylbutyrate
84
what is there a build up of in lysosomal storage disorders
unprocessed materials SLOWLY over time in the lysosome
85
are the symptoms/features of lysosomal storage disorders there at birth or progressive
progressive; kids are normal at birth
86
how are lysosomal storage disorders classified?
based on the type of molecule that builds up
87
2 types of lysosomal storage disorders?
lipid disorders and mucopolysaccharide disorders
88
what type of disorder is tay sachs disease
lysosomal storage disorder: lipid disorder (ganglioside 2)
89
what type of mutation is in tay sachs and what is the inheritance pattern
autosomal recessive mutation in HEXA
90
what enzyme are ppl with tay sachs deficient in
hexosaminidase A enzyme (HEXA)
91
what population is tay sachs most common in
ashkenazi jews
92
what do you get an accumulation of in tay sachs
ganglioside 2 (GM 2)
93
clinical presentation of tay sachs birth-6 months
progressive motor weakness, myoclonic jerks, exaggerated startle response
94
clinical presentation of tay sachs 6-10 months
cherry red macula, regression, dec. vision
95
clinical presentation of tay sachs 10+ months
dec. mvmt and responsiveness, seizures, deterioration
96
when do ppl with tay sachs usually die by
4 years old
97
what type of inheritance is gauchers disease
autosomal recessive
98
what enzyme is deficient in gauchers
glucerebrosidase
99
what population is gauchers MC in
ashkenazi jews
100
clinical features of gauchers
hepatosplenomegaly, anemia, thrombocytopenia, leukopenia, bone disease, bone crises, pseudo-osteomyelitis
101
what are the two types of gauchers disease
neurological and non neurological involvement
102
what is mucopolysaccharidoses (MPS) 1 called
hurler syndrome
103
what inheritance pattern is MSP 1/hurler?
autosomal recessive
104
what is mucopolysaccharidoses (MPS) 2 called
hunter syndrome
105
what inheritance pattern is MSP 2/hunter?
x linked recessive
106
what MSP syndrome is there corneal clouding
MSP 1/hurler
107
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
108
trmt for MSP disorders
enzyme replacement therapy, bone marrow transplant
109
what type of disorder is Lesch-Nyhan
disorder of purine (A-G) metabolism
110
what type of inheritance pattern is Lesch Nyhan
x linked recessive
111
what enzyme is there a deficiency in lesch nyhan
HGPRT 1
112
is Lesch-Nyhan an inborn error of metabolism
no
113
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
114
clinical symptoms of hyperuricemia
gout, orange crystals in diaper, kidney stones
115
who is MPS more common in: boys or girls
boys
116
do the symptoms for MPS come on acutely or are they progressive?
progressive: happen SLOW over time
117
is Lesch-Nyhan more common in boys or girls
boys bc its x linked
118
what is MTHFR
a gene commercially marketed to cause a variety of different disease processes including CV disease, cancer, preganancy loss, and thrombosis
119
what does MTHFR stand for and what is it involved in
methylenetetrafolate reductase which is involved in folate metabolism
