Although inborn errors of metabolism( IEM) are rare, early recognition of these disorders is important to prevent neurologic damage and institute therapy early.  Presenting signs and symptoms are confused with sepsis, central nervous system disorders, cardiac, respiratory, and gastrointestinal diseases.  The evaluation of the sick neonate must include the possibility of an IEM. 

Presenting symptoms of IEM
1. Lethargy 
2. Poor feeding and/or symptoms after feeding 
3. seizures 
4. persistent vomiting 
5. Tachypnea, Kussmaul breathing pattern, or apnea 
6. Jaundice and hepatolmegaly 
7. Hypotonia or spasticity 
8. Failure to gain weight 
9. Bleeding 
10. Neonate was usually normal at birth and no risk factors for sepsis 
11. Positive family history of early death or child with similar symptoms 
12. Parental consanguinity 
13.  Unusual body odors- maple syrup, sweaty feet, musty, rancid, cabbage smell 

Clinical Manifestations of IEM
1. Metabolic Acidosis- persistent vomiting, tachypnea, seizures, hypotonia 
  a. A metabolic acidosis with an anion gap > 16 
  b. Organic acidemias may also have an increase of ammonia, anemia, neutropenia, and thrombocytopenia 
  c. If there is no anion gap, think of metabolic acidosis secondary to diarrhea disease or renal tubular acidosis. 

2. Hyperammonia- altered consciousness, persistent vomiting, lethargic 
  a.  Venous sample and must be handled properly after drawing 
  b.. Diff Dx includes urea cycle defects (UCD), organic acidemias, liver disease, transient hyperammonia of the newborn (THAN), sepsis, TPN, valproic acid 
  c. With UCD, the levels are usually > than 1000umol/L, the other possibilities have lower ammonia levels and may be transient. 
  d. There may be a respiratory alkalosis 
  e. If there is an elevated ammonia without an increased anion gap, most likely have a UCD.  If there is an elevated ammonia with an increase in the anion gap, usually have an organic acidemia 

Laboratory evaluation for suspected IEM
1. CBC, differential, and platelets 
2. Serum electrolytes 
3. Arterial blood gas 
4. serum glucose 
5. Blood ammonia level 
6. Urine for reducing substances- R/O galactosemia 
7. Urine for ketones if the neonate is hypoglycemic or acidotic 
8. Urine and blood for amino acids 
9. Urine or organic acids 

Emergency Treatment
1. Removal of metabolites that are accumulating with dialysis 
2. Stop all protein ingestion 
3. Arginine infusion if suspect urea cycle defect 
4. B12 and biotin should be given if suspect organic acidemia 
5. Send appropriate labs 
6. Consultation with geneticist or metabolic specialist. 
7. If the patient is dying, it is important to obtain appropriate materials for diagnosis.  Urine and separated plasma should be frozen, a tissue sample must be obtained and placed in special medium, and a needle biopsy of the liver should be gotten. 

Common IEM
1. Organic Acidemias
  a. Methyl malonic acidemia 
  b. Propionic acidemia 
  c. Multiple carboxylase deficiency
  d. Isovaleric acidemia 
  e. Maple syrup urine disease 
2. Urea Cycle Defects
  a. Orntihine transcarbamylase deficiency 
  b. Arginosuccinic aciduria 
  c. Citrullinemia 

References
1. Burton BK.  Inborn Errors of Metabolism in Infancy: A guide to Diagnosis.  Pediatrics. 1998; 102(6):e69. 
2. Ward, Jewell. Inborn Errors Of Metabolism of Acute Onset In Infancy.  Pediatrics in Review Vol. 11 No. 7 January 1990
3. Debray F. et al. Long-term Outcome and Clinical Spectrum of 73 Pediatric Patients With Mitochondrial Diseases. Pedicatrics April 2007