View source for Inborn errors of metabolism

==Background==
*Clinical manifestations are due to accumulation of toxic metabolites
*Suspect in any sick neonate
*Newborn screening varies by state
*May present as late as early adulthood 
*Must rule-out [[sepsis (Peds)|sepsis]] (more common in these patients due to organic acid-induced bone marrow suppression) and other physiologic stressors that might be precipitating decompensation

==Clinical Features==
Varies depending on disorder
*Lethargy, [[Altered mental status (peds)|AMS]], [[encephalopathy]] (often [[hyperammonemia|hyperammonemic]])
*[[Seizure]]
*Hypotonia 
*[[Nausea]]/[[vomiting]], [[diarrhea]]
*Difficulty feeding
*[[Failure to thrive (peds)|Failure to thrive]]
*Unusual odors 
*[[hypoglycemia (peds)|Hypoglycemia]]
*Organomegaly
*+/- Skin [[rashes (Peds)|rashes]]
*+/- Eye findings
*Signs/symptoms of [[dehydration (peds)|dehydration]]
*Infections

==Differential Diagnosis==
{{Sick neonate DDX}}

==Evaluation==
*Evaluate for metabolic derangement +/- precipitant of decompensation
*Labs:
**'''Glucose''' level (most important/time sensitive!)
**[[Ketonemia|Ketones]] (urine or serum beta hydroxybutyrate)- helpful to obtain prior to giving [[dextrose]] in hypoglycemic patients, if possible
**Ammonia
***Should be <100 in normal neonate
**BMP, [[LFTs]]
***Anion gap (if >20, suggests an organic acidemia)
***May see hypoglycemia, [[metabolic acidosis]]
**[[VBG]]
**[[Lactate]] and pyruvate (drawn at same time)
**CBC 
**Blood culture, urine culture, +/- [[CSF]]
**Additional tests to aid in definitive diagnosis (consider setting aside blood sample on ice prior to dextrose admin)
***Muscle function tests (e.g. CPK, LDH, myoglobin)
***Serum/plasma pyruvate, amino acids, acylcarnitine profile
***Urine organic acids, acylglycines, orotic acid
*Consider [[head CT]] (evaluate for cerebral edema and alternate etiologies of symptoms)
*Evaluate for alternate etiologies 

==Management==
*Patients with diagnosed inborn errors often have pre-established plans for "sick day" or emergency guidance
*Early consultation with specialists

===[[neonatal resuscitation|Resuscitate]], stop catabolism/accumulation of toxins===
*Keep NPO
**Removes potential inciting metabolic substrates
*IVF
**[[Normal saline]] 10-20 mL/kg boluses
***Reassess after each bolus, as [[congenital heart disease]] may mimic symptoms of inborn errors
**IVF with [[dextrose]] (D10) and 0.45 or 0.9% NS at 1.5-2x maintenance
***Aggressive hydration increases urinary excretion of toxic metabolites, dextrose provides metabolic substrate

===[[Hyperammonemia]]===
*<500 micromoles/L
**[[sodium phenylacetate/sodium benzoate]] (Ammonul) 250mg/kg in D10 over 90min; then 250mg/kg/d infusion
**Arginine 210mg/kg IV/IO in D10 over 90min; then 210mg/kg/d infusion
**+/- [[levocarnitine|carnitine]], 400 mg IV/IO in consultation w/specialist
**May require [[dialysis]] if refractory/severe

===[[Acidosis]]===
*Sodium [[bicarbonate]] 0.5 mEq/kg/h if pH <7.0 <ref>Tintanelli's</ref>
**Reserve for severe and/or refractory acidosis due to potential side effects of sodium overload, cerebral edema, cardiac dysfunction
*Caution intubating any child in metabolic crisis due to potential worsening of acidosis 

===Cerebral edema===
*Hyperammonemia is risk factor
**[[Mannitol]] 0.5gm/kg IV/IO
**Do '''not''' give steroids (worsens hyperammonemia)

===[[Seizure (peds)|Seizure]]===
*Consider [[vitamin B6]] (pyridoxine) in addition to usual care

===Infection/[[Sepsis (peds)|Sepsis]]===
*Consider empiric [[Pediatric antibiotics|antibiotics]] in all infants in metabolic crisis

==Dispo==
*Admit or transfer to tertiary care children's hospital

==See Also==
*[[Neonatal Resuscitation]]

==References==
<references/>

[[Category:Pediatrics]]
[[Category:Endocrinology]]