newborn screening tests lab med

a system to identify disorders (genetic/developmental/metabolic) as early as possible. these are state specific, may be specifically opted out of at parents request, and are NOT diagnostic,

Newborn Screening tests

what is the focus of newborn screening testing

disorders with effective early intervention

what are some of the challanges of running newborn screening tests

restricted blood volume, lack of appropriate reference values, disorders unique to the newborn

what are the basic testing methods and components of a newborn screening test

enzyme linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), colorimetric assay, tandem mass spectrometry, DNA

use hearing screen and dried bloodspot tests as components

what is the purpose of newborn screening tests

to improve longterm outcomes via early diagnosis and treatment

what are the criteria for a disease to be tested in the newborn screening panel

disease has sufficiently high frequency in a pop

disease prevalence in specific groups is well documented

disease is readily treatable

screening test readily available on blood spots

screening cost isnt insane

high sensitivity tests

high specificity tests

high cost to society if the disease is untreated

when we do we do a newborn screening panel

24-48hrs after birth and 1-2 weeks after birth

are newborn screening tests legally required (unless parents opt out)

yes (tx law requires these lab tests to help find infants who may have one or more of the disorders or medical conditions tested)

where do we draw blood from babies for the newborn screening panel and how

from the sides of the bottom of their heel, drop several drops of the blood into specific spots on the special paper and then ship it to the lab (aseptic collection)

if we have to do a screening test on an older kid what should they do before hand

be on their normal diet and fast 6-8hrs before hand and well collect blood and urine samples in the same appt

if were screening an older kid what kind of tubes will we use for the blood samples

heparin tubes

what factors can affect blood collection results in older kids

age at collection, prematurity, meds, diet, maternal conditions, collection method, ambient temp/humidity, time at transit to lab

what is done w the specimens (little blood spots) after collection for a newborn screening panel

kept for up to 2yrs and then destroyed unless parents opt out of it being stored

inherited or mutation born failures of metabolic pathways

inborn errors of metabolism

3 categories of inborn errors of metabolism

protein metabolism disorders, fatty acid oxidation disorders, carb metabolism disorders

what can happen if we dont catch inborn errors of metabolism soon enough

can lead to intellectual/developmental delays, physical or neurological disabilities or death if untreated

do infants born with inborn errors of metabolism often have sx right at birth

no sx at first but sx are apparent within just a few months w/o tx

common general sx for inborn errors of metabolism

poor feeding, dec responsiveness, lethargy, dec muscle tone, seizures, vomiting, developmental delays, coma

when do we strongly suspect inborn errors of metabolism

fmily hx of similar illness/death

hx of clinical deterioration in previously normal baby

developmental delay or regression

sx accompany changes in diet (difficulty or refusal to feed or puking)

hx of food preferences or aversions

protein metabolism disorders

PKU, tyrosinemia (type 2), maple syrup urine disease, homocystinuria

carb metabolism disorders (discussed here)

galactosemia

a rare autosomal recessive disorder but still the most common inborn error of metabolism that is a deficiency of phenylalanine hydroxylase (PAH)

phenylketonuria (PKU)

what causes PKU

no phenylalanine hydroxylase → cant metabolize amino acid phenylalanine → phenylalanine accumulates and gets toxic

complications that can arise from PKU

damages the nervous system and can cause intellectual disability, psychiatric disorder or seizures (still full life expectancy with or w/o tx)

what can you find find the amino acid phenylalanine in

any food w protein

what would a positive test for PKU on the newborn screening panel look like and what would we do next

phenylalanine over 20mg/dL and LOW tyrosine

gotta get a confirmatory test

sx of PKU

small head size, seizures, developmental delays, intellectual disabilities, tremors/jerking movements in extremities, hyperactivity, stunted growth, skin rashes (eczema), musty odor (on breath/urine/skin), fair skin and blue eyes

dietary tx for PKU

reduce natural protein intake, eat vitamins, minerals, and antioxidants (basically just eat fruits and veggies, sugars, and special breads/crackers etc), can supplement w special formulas

drug tx for PKU

Kuvan (must be used w low phenylalanine diet, improves innate phenylalanine hydroxylase enzyme activity and inc phenylalanine tolerance)

palynziq (metabolizes phenylalanine and good for adults)

what confirmatory tests can we do for PKU

guthrie’s test (newborn blood sample to test for bacillus subtillus)

FeCL3 test (PKU makes it turn blue/green, not specific)

prenatal diagnosis (requires molecular testing and amniocentesis)

a rare autosomal recessive inherited disorder common among french Canadians that is a deficiency in tyrosine aminotransferase

tyrosinemia (type 2)

what causes tyrosinemia type 2

no tyrosine aminotransferase → cant metabolize amino acid tyrosine → accumulation in blood gets toxic

complications of tyrosinemia type 2

premature or low bodyweight in babies, skin/eye/intellectual problems, progresses to liver and kidney damage

tyrosinemia type 2 tx

low protein diet (no foods w tyrosine, can supplement w special formulas

diagnostic testing for tyrosinemia type 2

high tyrosine on blood test

high tyrosine and high tyrosine metabolites on urine test

genetic study will see TAT mutations

tyrosinemia type 2 sx

corneal ulcers (leads to light sensitivity)

corneal opacity

palmar and plantar hyperkeratosis

hyperhidrosis (hella sweaty hands)

a rare autosomal recessive disorder that inc in pops w a small gene pool (mennonites) that is a deficiency in brannched-chain alpha-ketoacid dehydrogynase

maple syrup urine disease

what causes maple syrup urine disease

no branched-chain alpha-ketoacid dehydrogenase (BCKAD) → cant break down branched chain amino acids (BCAAs) → builds up and gets toxic

complications of maple syrup urine disease

overwhelming illness on 1st day of life, acidosis, vomiting, developmental delays, CNS disorders, coma, death

maple syrup urine disease tx

dietary restriction of leucine, isolucine, and valine (can supplement w special formulas)

if we take a urine sample from a pt w maple syrup urine disease what will we see

looks dark brown/redish, burnt sugar odor, HIGH levels of leucine, isoleucine, and valine

maple syrup urine disease sx

lack of appetite, lethragy, slim down, poor sucking ability, characteristic smell of sweat/earwax/urine like maple sugar, hypertonia/hypotonia, irritability, loud cry, pancreatitis/pancreas enlargement, hepatitis/liver enlargement, seizures, bad growth, loss bone mass, developmental delays, feeding issues

an autosomal recessive disorder that is a deficiency in cystathionine synthase

homocystinuria

what causes homocystinuria

no cystathionine synthase → cant metabolize amino acid homocysteine from methionine → homocysteine builds up and gets toxic

complications from homocystinuria

damage to the eyes, skeletal system, central nervous system, and vascular system which can lead to intellectual disability, bone disease, and blood clots

homocystinuria tx

pyridoxine, low methionine diet

sx of homocystinuria

anxiety, dislocated lenses, high arched palates and crowded teeth, mild scoliosis, osteopenia, osteoarthritis, fair slin, long limbs, pectus carninatum, blood clots (esp wrist), GI issues, sensitive skin, tremors, hx of depression/OCD/ADHD/outbursts/sensory processing problems, trouble making eye contact

how can we control homocystinuria sx

vit B6 supplement or pyridoxine, diet low in methionine, metanine meds (dec homocystine levels)

an autosomal recessive genetic disorder that is a deficiency in galactokinase or galactose-1-phosphate uridylytransferase

galactosemia

what causes galactosemia

no galactokinase or galactose-1-phosphate uridylytransferase → cant break down galactose to glucose → cant use galactose to produce energy → galactose buildup gets toxic

galactosemia complications

dangerous if metabolites stored in large mounts in the liver, brain, kidneys, or other organs

galactosemia tx

galactose and lactose free diet

galactosemia sx

brain damage, cataracts, jaundice, enlarged liver/liver failure, kidney damage (can lead to coma and death)

what endocrine disorders are screened for in the newborn screening panel

congenital hypothyroidism (cretinism), congenital adrenal hyperplasia