Inborn errors of metabolism: Difference between revisions

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==Background==
==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


Over hundreds of diseases
==Differential Diagnosis==
{{Sick neonate DDX}}


Suspect in any sick neonate
==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


Newborn screening varies by states, California tests for 29 major diseases
==Management==
*Patients with diagnosed inborn errors often have pre-established plans for "sick day" or emergency guidance
*Early consultation with specialists


May present as late as early childhood
===[[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


==Diagnosis==
===[[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)


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


* Lethargic (2/2 hyperammonia encephelopathy)
===Infection/[[Sepsis (peds)|Sepsis]]===
* Nausea/vomiting
*Consider empiric [[Pediatric antibiotics|antibiotics]] in all infants in metabolic crisis
* Difficulty feeding
* Seizure
* Strange odors
* Hypotonia


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


Elevated Ammonia
* Key to suspect diagnosis, however there are a few diseases where  ammonia may be normal
* +/- Hypoglycemia, metabolic acidosis, anion gate, elevated  lactate, ketones
Sepsis work up usually concomitant, if patient is ill as these children are prone to infections
==DDx==
in neonates: THE MISFITS
see Neonatal Resuscitation
==Treatment==
Must stop catabolism and acculmulation of toxins/ammonia
* IVF with Dextrose at 1-1.5x maintenace
* Don't feed
* Dialysis (ammonia >500)
* NaBicarb if acidotic
* Consider L-carnitine in conjuction with specialist, as some diseases may respond (but has side effects)
* Antibiotics-- assume sepsis
* if seizing-- consider Vit B6/pyroxidine
* 
==See Also==
==See Also==
*[[Neonatal Resuscitation]]


==References==
<references/>


see Neonatal Resuscitation
[[Category:Pediatrics]]
 
[[Category:Endocrinology]]
 
 
 
 
[[Category:Peds]]

Latest revision as of 05:04, 21 April 2021

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 (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

Differential Diagnosis

Sick Neonate

THE MISFITS [1]

Evaluation

  • Evaluate for metabolic derangement +/- precipitant of decompensation
  • Labs:
    • Glucose level (most important/time sensitive!)
    • 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
    • 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

Resuscitate, stop catabolism/accumulation of toxins

  • Keep NPO
    • Removes potential inciting metabolic substrates
  • IVF
    • Normal saline 10-20 mL/kg boluses
    • 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
    • +/- 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 [2]
    • 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

  • Consider vitamin B6 (pyridoxine) in addition to usual care

Infection/Sepsis

  • Consider empiric antibiotics in all infants in metabolic crisis

Dispo

  • Admit or transfer to tertiary care children's hospital

See Also

References

  1. ↑ Brousseau T, Sharieff GQ. Newborn emergencies: the first 30 days of life. Pediatr Clin North Am. 2006 Feb;53(1):69-84, vi.
  2. ↑ Tintanelli's
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