ohio newborn screening Flashcards
avg annual birthrate in ohio since 1990
135,000
how did ohio metabolic NBS program begin
they screened for PKU as a trial and then it expanded to a mandated statewide program in 1965
where is the NBS lab in ohio located
Reynoldburg
why are most specimens inconclusive
sample at less than 24 hrs of age (too early) and time of collection missing
what is not included in the ohio NBS panel
nonketotic hyperglycinemia bc its lethal so theres no reason in screening for it
what can ppl with galactosemia not convert
glucose to galactose
inheritance pattern of galactosemia?
autosomal recessive
trmt for galactosemia?
galactose free diet
what is glucose + galactose
lactose
what does galactosemia lead to
immediate liver damage, sepsis
what disorders does the enzyme assay technique screen for
biotinidase deficiency, galactosemia, LSDs (Krabbes, MPSI, Pompe)
what disorders does the isoelectric focusing/capillary HPLC (high performance liquid chromatographies) technique screen for
hemoglobinopathies
what disorders does the immunoflourometric technique screen for
hypothyroidism, congenital adrenal hyperplasia (CAH), CF
what is the biggest take away from an enzyme assay test
you dont need to wait 24 hours to test
what happens if there is an abnormal result in NBS
it must be repeated
turn around time for NBS?
5 days
biotinidase?
enzyme that recycles biotin
inheritance pattern of biotinidase deficiency?
autosomal recessive
biotinidase deficiency disorder?
disorder of biotin recycling that causes a deficiency in biotin and multiple carboxylase deficiencies (bc biotin is a cofactor for many carboxylase rxns)
trmt for biotinidase deficiency
daily biotin supplement which makes the disease basically curable
we do HPLC for hemoglobinopathies rn, but what did we do before?
isoelectric focusing but with new technological advances we dont do this anymore)
mc abnormalities on newborn screenings?
thyroid diseases (hypothyroidism mainly)
why is it important to get the timing of congenital hypothyroidism screening correct
TSH surge occurs shortly after birth and may give a false positive result if sample is obtained in 1st 24 hours
what are positive samples of congenital hypothyroidism reanalyzed for
T4
what is measured to test for congenital hypothyroidism
TSH
what is there a defect in in congenital adrenal hyperplasia
cortisol synthesis; most commonly 21-hydroxylase deficiency
inheritance pattern for congenital adrenal hyperplasia
autosomal recessive
who is congenital adrenal hyperplasia very common in
prematures
what is the analyte measured in congenital adrenal hyperplasia
17-OH progesterone
what disorder is weight dependent meaning you need to know the weight to understand the results
congenital adrenal hyperplasia
what disorder is different for males and females? Females have verilization and males have cardiac distress
CAH
what do babies with PKU look like at birth
normal
what can PKU look like if untreated
irreversible mental retardation
inheritance pattern of tyrosinemia type 1
autosomal recessive
what disorders are screened for with tandem MS/MS techniques
PKU, tyrosinemia type 1
what does untreated tyrosinemia type 1 lead to
hepatocarcinoma
what is tyrosinemia type 1
fumarylacetoacetase enzyme deficiency in tyrosine degradation pathway
what is the analyte measured in tyrosinemia type 1
succinylacetone
trmt for tyrosinemia type 1
NTBC (medication) and liver transplant
what is the toxic compound formed in tyrosinemia type 1
succinylacetone
clinical features of tyrosinemia type 1
liver failure, cirrhosis, hepatocellular carcinoma, episodic neuropathy
MC metabolic disorder youll see in primary care setting?
fatty acid oxidation defects
inheritance pattern for fatty acid oxidation defects?
autosomal recessive
what are fatty acid oxidation defects?
disorders involving multiple steps in the degradation pathway of fatty acids in mitochondria
what do fatty acid oxidation defects usually present with
hypoketoic hypoglycemia and hyperammonemia
MC fatty acid oxidation defects?
MCAD deficiency
why are fatty acid oxidation defects so dangerous?
fatty acids can accumulate in the blood and inhibit body from making sugar
trmt for fatty acid oxidation defects?
dietary fat restriction and L-carnitine
baby aspirin increased the number of cases in which disorder
fatty acid oxidation defects
analyte measured in fatty acid oxidation defects?
acylcarnitine ester
inheritance pattern in cystic fibrosis
autosomal recessive
what is cystic fibrosis
chloride channelopathy resulting in lethal pancreatic, pulmonary disease
analyte measured in cyctic fibrosis
immunoreactive trypsinogen (IRT)
trmt for cyctic fibrosis
support
what is the 2nd tier testing of cystic fibrosis
DNA testing
what does SCID stand for
severe combined immune deficiency
what does TREC stand for
t cell receptor excision circle
in this disorder once babies get an infection they usually die
SCID
how does the lab look at SCID?
they use PCR to amplify TREC if its there. If its not there, the babies get sent to immunology for further testing
inheritance pattern in spinal musclular atrophy (SMA)
autosomal recessive
what are most cases of SMA due to
homozygous SMN 1 gene deletion (both copies)
what can SMA lead to if not treated
early lethality from progressive paralysis
trmt for SMA
medication
when must trmt for SMA be started
before death of spinal anterior horn cells
what is C5OH
a marker for such as 3 methylcrotonly carboxylase deficiency, a disorder of leucine metabolism. 50% of high risk alerts are due to an affected mother
what is C3?
a marker for propionic/methylmalonic acidemia that can also be seen in maternal vitamin B12 deficiency, especially in vegans
what is C0?
low free carnitine is the marker for a carnitine uptake disorder which can result in hypoketotic glycemia and cardiomyopathy in newborns. In 50% of cases, mothers are affected with CUD
should you ever draw NBS samples from TPN or IV line
NO bc false + may occur
what disorder is the timing of sample acquisition very important
endocrine, hypothyroidism, CAH, disorders of amino, organic, and fatty acids
what disorder is the timing of sample acquisition not important for
enzyme assays like biotinidase, galactosemia, LSD, hemoglobin disorders, CF, SMA, DMD, and SCIDS
what disorders typically normalize after the 1st week of life so if you dont test for it before hand its hard to catch
FAOD
who is ethically and legally responsible for follow up NBS results
physician of record even if theyve never seen them
what happens if a pt cant be located
the ODH lab must be notified by phone AND writing
what is the MS collaborative project useful for
quantitating the degree of a risk and the liklihood of a false positive, although it’s NOT diagnostic
cost of NBS in ohio
$74.61
what does the NBS cost go towards
lab tests, regional genetic centers, sickle cell programs, PKU program, CF program
does it cost a lot more money for false positives or any alerts
YES
why are some diseases not tested for in NBS
cost, no effective therapy, not common in kids or more in older ppl
what type of disorder is pompes disease
disorder of lysosomal glycogen degradation
what is pompes disorder a deficiency in
alpha glucosidase
clinical features of pompes
progressive hypotonia, cardiomyopathy, respiratory failure, death by age 1 if not treated
trmt for pompes
enzyme replacement therapy
what is the ONLY disorder mandated by legislature to screen for
Krabbe disease
what is MPS1- hurlers syndrome a deficiency in
alpha iduronidase
clinical features of hurlers
corneal clouding, hepatosplenomegaly, coarse features, macroglossia, joint limitation, valvular heart disease, dysostosis multiplex, deafness
trmt for hurlers
enzyme replacement therapy (ERT) and BMT
inheritance pattern for krabbes
autosomal recessive
what is there a deficiency in for krabbes
galactocerebrosidase enzyme
when do infantile cases have symptoms of krabbes
before 6 months
infantile symptoms of krabbes?
irritability, loss of head control, fever, feeding trouble, emesis, muscle spasms, progressing to seizures, atazia, blindness
galactolipid accumulation in krabbes is a directly toxic to what
myelinated cells
what can you see on krabbes MRI of brain
severe demyeliation
where is gene of krabbes located?
14q13 deletion (about a 30 kb deletion)
what is pseudodeficiency?
when someone cannot metabolize the artificial substrate to an enzyme but the can metabolize the normal one. so it looks like they have the disease
