Newborn Screening Tests

Newborn Screening (NBS)

A system to identify disorders as early as possible

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

What are some challenges of NBS

hearing screen, dried bloodspot test

What are the parts of NBS

enzyme-linked immunosorbent assay, high-performance liquid chromatography, colorimetric assay, tandem mass spectrometry, DNA

What laboratory methods are used in NBS?

high incidences, well documented prevalence, readily treatable, available on blood spots, costs not prohibitive, high sensitivity, high specificity, high cost to society if not treated

What are the criteria for which disorders we do NBS testing?

2 rounds of testing (first on 24-48 hr birth, then 2 weeks later)

In Texas, what are the NBS requirements?

Collected via heel stick usually on special filter paper, then dried, and mailed

Describe how NBS testing works?

Normal diet, collect fasting blood and urine sample, heparin tube (amino acid and leucocytes), store frozen

Rules for screening an older child

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

Factors that affect the results of an NBS

Between 24-72 hours of age

When should collection of newborn blood spot screening occur

within 72 hours of collection

When should transportation of newborn blood spot screening occur

within 96 hr of lab receipt

When should reporting of newborn blood spot screening occur

amino acidopathies (PKU, TYR, HCU, MSUD), organic acaidaemias (MMA/PA, IVA, GA), Urea cycle disorders (OTC, ASL, CPS, HHH, CTLN1, ARG, CTLN2, NAGS)

What are some of the protein metabolism disorders?

long chain fatty acid oxidation disorders, medium chain fatty acid oxidation disorders, short chain fatty acid oxidation disorders

What are some of the fatty acid oxidation disorders?

glycogen storage disease, galactosemia, fructose metabolism disorder, pyruvate metabolism disorders

What are some of the carbohydrate metabolism disorders

poor feeding, decreased responsiveness, lethargy, decreased muscle tone, seizures, failure to gain weight and grow, vomiting, developmental delay, coma

What are some common symptoms of inborn errors of metabolism

Family hx of similar illness, hx of clinical deterioration, developmental delay or regression, symptoms accompany changes in diet, hx of food preferences

Red flags for inborn errors of metabolism

PKU (phenylkeyonuria)

What is an autosomal recessive disorder, is the most common IEM, and results in the inability to metabolize phenylalanine?

Phenylalanine hydroxylase (PAH)

PKU is a deficiency of _______________

damage to nervous system (intellectual disability, psychiatric disorders, seizures)

Complications of PKU

confirmatory testing

If a NBS pops positive for PKU, what do we need to do

reduction of natural protein intake, special PKU formula

3 week old baby present to the clinic with failure to thrive. On a physical exam you note tremors/jerking movements, hyperactivity, a small head, eczema, and a musty odor. The child is small for their age and is not meeting developmental stages. Lab works shows elevated phenylalanine in the blood. What is your treatment plan?

Kuvan, palnziq

What are some pharmaceutical treatments for PKU which act similar to the PAH enzyme?

Guthrie’s test, FeCl3 (not specific), prenatal testing (amniocentesis, molecular testing)

Diagnostic test for PKU

Tyrosinemia (type II)

What is an autosomal recessive disorder common in French-Canadians that is characterized by an inability to metabolize tyrosine?

TAT (tyrosine aminotransferase)

What is the deficiency in Tyrosinemia (type II)

premature/low birth weight babies, skin, eye, intellectual problems, liver/kidney damage, rapidly fatal

Complications of Tyrosinemia (type II)

Blood or urine studies (high tyrosine), genetic testing (TAT mutations)

Ways to confirm Tyrosinemia (type II)

low protein diet, special formulas

3 week old baby presents to the clinic for failure to thrive. On a physical exam you note corneal ulcers, palmar and plantar hyperkeratosis, and as well as hyperhidrosis. What is your treatment plan

Maple syrup urine disease (MSUD)

What autosomal recessive disorder common in Mennonites is characterized by an inability to break down branched chain amino acids?

branched-chain alpha-ketoacid dehydrogenase (BCKAD)

Deficiency in MSUD

Present on day 1 of life, acidosis, vomiting, developmental delays, CNS disorder, coma, death

Complications of MSUD

dietary restriction of leucine, isoleucine, valine

3 week old presents to the clinic for failure to thrive. Mother reports lack of appetite and difficulty suckling. On physical exam you note lethargy, a smell of burnt sugar, hypertonia/hyponia, and a loud cry. Lab work shows elevated leucine, isoleucine and valine what is your treatment plan?

Homocystinuria (HCU)

What is an autosomal recessive disorder that is characterized by an inability to metabolize homocysteine from methionine?

damage to eyes, skeletal system, CNS, and vascular system; intellectual disability, bone disease, blood clot

Complications of HCU

Cystathionine synthase (CBS)

What is the deficiency in HCU

B6 or pyridoxine supplements, low methionine diet, Betaine (last)

Patient presents to the clinic for GI issues. She also reports sensitive skin and anxiety. PMHx is positive for esotropia, depression, OCD, and ADD. On a physical exam you note fair skin, long extremities, pectus carinatum, and mild scoliosis. Lab work shows elevated levels of homocysteine in the blood and urine. What is your treatment plan?

Galactosemia

What is an autosomal recessive disorder characterized by the inability to breakdown and use galactose?

Galactokinase (GALK) OR Galactose-1-phosphate urydylytransferase

What is deficiency in galactosemia?

Metabolites get stored in liver, brain, kidney, and other organs which causes PROBLEMS

Complications of Galactosemia

Restriction of galactose and lactose

3 week old presents to the clinic for failure to thrive. On physical exam you note enlarged liver, cataracts and jaundice. Lab work shows elevated BUN, Creatinine, AST, ALT, as well as increased blood galactose. What is your treatment plan?

congenital hypothyroidism, congenital adrenal hyperplasia

What are the 2 endocrine disorders we screen for at birth?