Newborn Screening Flashcards
What is NBS?
Guthrie spot
heel stick blood
tests for 60 conditions in NY state (all states test for at least 29)
began in 1961
What is PKU?
phenylketonuria
deficiency of PAH enzyme that breaks down phenylalanine
high Phe is neurotoxic (goal Phe level is 2-6) leading to severe ID, seizures, and neurological problems
treatable with low Phe diet
What is Hyperphe?
mild form of PKU where PAH enzyme activity is greater and phe levels are typically lower
same gene
What are the criteria for conditions to be screened for on NBS?
the condition can be detected 24 to 48 hours after birth, when it cannot usually be detected by a doctor’s exam
It has a test that is specific and sensitive for the condition
Its early detection, timely intervention and effective treatment offer proven benefit
Describe the NBS process.
baby born
heel stick blood collected in hospital
NBS card sent to a state health department lab
if ABNORMAL screen is sent to a designated center based on which condition and what hospital the baby was born at
family contacted to go in for repeat testing at designated center
if true POSITIVE (many are false positives), establish care
*note that most screens are negative/normal and results are mailed to the family
What are the psychosocial concerns surrounding NBS results disclosures?
the setting ( someone just had a baby- which is stressful in itself- and discussing potential genetic disorders can be difficult especially if they aren't apparent at birth) the set up (places that calls the family with the news may not be where the baby was born) the context (most people don't know NBS exists, much less what it means when it's abnormal) the limitations (this is a SCREENING not diagnostic test)
List some drawbacks of NBS.
pseudodeficiency alleles (variants that, in the lab cause low enzyme levels but not in patients)
hyperphenylalanemia
definition of “effective treatments” is unclear
administrative and economic burden of treatments available may not be reasonable for all families
What is XALD?
ABCD1 gene
XL inheritance
dysfunction in processing of VLCFA which can be detected on NBS
List the categories of manifestations of XALD.
childhood cerebral form
adrenomyeloneuropathy (AMN)
Addison disease
What symptoms are associated with female carriers of XALD?
spastic paraparesis and urinary issues in middle age
gradual weakness with muscle spasms (spastic weakness) in legs
exaggerated reflexes, cramps, and spasms that make walking difficult
What difficulties are experienced in practice with patients with XALD?
spectrum- manifests in many ways at any time (from asymptomatic to severe cerebral presentation)
detection of females who, if they develop symptoms, may begin manifesting milder symptoms in middle age
no consensus on the frequency of screening and monitoring
How is XALD treated?
BMT- effective in the childhood cerebral form
note that high morbidity means that it is only recommended for those developing white matter changes
MUST be done within therapeutic window
What incidental findings can mimic XALD?
VLCFA elevation is also caused by peroxisomal disorders that do not have known treatments or effective therapies
purpose of the NBS is to detect treatable disorders that manifest in infancy/early childhood, however by looking for one of those disorders with available interventions, we can (and do) find people affected with progressive, fatal diseases without those helpful interventions
What are the long term follow-up recommendations for XALD?
no guidelines, just guidance
annual MRI and frequent endocrine blood work/evaluations
balance between losing females to follow-up and medicalizing healthy children
What are some things to keep in mind that are nuanced for metabolics?
conditions on the NBS are chosen in part because of easy and cost-effective detection (as a result, most are metabolic disorders)
simple concept, but as NBS programs expand, more complicated in practice
when seeing a patient in a metabolic setting understand WHEN and WHERE they were born and what CAN and CANNOT be detected through NBS
