IEMS & NBS Flashcards
What are IEMs?
Genetic disorders (Inborn) resulting from disruption of normal
metabolic pathways
* Typically, mutations in enzymes
What is the inheritance of IEMs?
Typically AR
Occasionally X-Linked Recessive
Rarely AD
What is the incidence of IEMs?
Rare individually, substantial in aggregate
Overall, ~1,500 newborns
What is involved in IEM Work-Up?
Empiric Initial Labwork:
* Electrolytes, Liver Functions, Urinalysis, Reducing Substances, Arterial Blood Gas, Complete
Blood Counts, Blood Cultures
* Plasma Amino Acids
* Urine Organic Acids
* Acyl-Carnitine profile (FAB)
* Very Long Chain Fatty Acids
* Ammonia, Lactic Acid & Pyruvate
Secondary testing:
* Imaging- MR SPECT
* Biopsy- Liver, Muscle, Fibroblast
* For Enzyme Activity, Microscopic Analysis
* Molecular Testing
* Single gene, Gene panel
Additional samples:
- Urine, Blood, CSF, Amniotic Fluid, Chorionic Villi
AXIOM: Test Rapidly; Treat Rapidly; Check Newborn Screen!
How does phenotype correlate with severity of IEMs?
Correlation with residual enzymatic
activity and level of accumulated
substrate/product deficiency
* Earlier onset disease = lower
residual enzyme activity = more
severe/faster course
* Later onset = higher residual
enzyme activity = less
severe/slower course
* However, this is not always the
case!
Small increases in enzyme activity
or reduction in substrate can have
large effects on the clinical
phenotype/outcome
Clinical Presentation of IEMs
Neonatal encephalopathy >35 weeks gestation
- stroke
- HIE
- Other: infection, malformation, metabolic, trauma
- Brainstem damage
Poor feeding
Vomiting/diarrhea
Dehydration
Hypotonia
Respiratory distress/tachypnea
Lethargy/coma
Seizures
Death
What are initial misdiagnoses of IEMs?
- Sepsis/infections
- Hypoxia/HIE
- Pyloric stenosis
- Formula intolerance
What biochemical testing makes up newborn screening?
Amino acids + acylcarnitine profile
