Inborn Errors of Metabolism Treatment & Management
- Author: Debra L Weiner, MD, PhD; Chief Editor: Stephen Kemp, MD, PhD more...
Access and establish airway, breathing, circulation.
Emergency Department Care
Delay in recognition and treatment may result in long-term neurologic impairment or death. Initiate treatment as quickly as possible.
Initial ED treatment does not require knowledge of the specific metabolic disease or even disease category (see Emergent treatment below). In any critically ill child, airway, breathing, and circulation must be established first. Hypoglycemia, acidosis, and hyperammonemia must be corrected. Consider antibiotics in any child who may be septic.
Goals of treatment
Goals of treatment for patients with an inborn error of metabolism (IEM) are prevention of further accumulation of harmful substances, correction of metabolic abnormalities, and elimination of toxic metabolites. Even the apparently stable patient with mild symptoms may deteriorate rapidly with progression to death within hours. With appropriate therapy, patients may completely recover without sequelae.
Start empiric treatment for a potential inborn error of metabolism as soon as the diagnosis is considered. Treatment of patients with a known inborn error of metabolism should be disease and patient specific. Families may have treatment protocols with them developed by an IEM specialist. They may also have instructions for what resuscitation measures should be given if resuscitation is necessary. Protocols for acute illness are available on the New England Consortium of Metabolic Programs.
See the following steps:
Access and establish airway, breathing, circulation: D10 normal saline should be used as bolus fluid unless the patient is hypoglycemic in which case, dextrose should instead be given as a bolus as detailed below. Avoid lactated Ringer's solution. Avoid hypotonic fluid load due to the risk of cerebral edema, particularly if hyperammonemia is present.
Discontinue oral intake in patients with decreased level of consciousness and patients who are vomiting.
Eliminate intake or administration of potentially harmful protein or sugars, especially galactose, fructose. Disease-specific offending agents should be eliminated for those with known IEM and those with positive newborn screen results.
Correct hypoglycemia, prevent catabolism, and promote urinary excretion of toxic metabolites.
- Correct hypoglycemia, if present, with IV dextrose bolus, as D10 for neonates and D10 or D25 beyond the neonatal period, 0.25-1 g/kg/dose, not to exceed 25 g/dose, and followed by continuous IV administration of dextrose.
- For all patients in whom IEM cannot be ruled out, give dextrose 10% IV at 1-1.5 maintenance (7-8 mg/kg/min) to keep glucose level at 120-150 mg/dL, which should prevent catabolism. High-volume maintenance fluid will also promote urinary excretion of some toxic metabolites.
- Add insulin, 0.2-0.3 IU/kg, as needed to maintain glucose level in the desired range.
Correct metabolic acidosis and electrolyte abnormalities.
- Sodium bicarbonate or if the patient is hypokalemic, potassium acetate, should be administered to correct acidosis. The pH (< 7.0-7.2) and dose 0.25-0.5 mEq/kg/h (up to 1-2 mEq/kg/h) IV at which sodium bicarbonate or potassium acetate should be administered are controversial because data are lacking. Rapid correction or overcorrection may have paradoxical effects on the CNS. For intractable acidosis, consider hemodialysis.
- Add electrolytes at maintenance concentrations, with appropriate adjustments to correct electrolyte disturbances if present.
Correct hyperammonemia. Significant hyperammonemia is life-threatening and must be treated immediately upon diagnosis.
- To reduce ammonia, sodium phenylacetate and sodium benzoate (Ammonul; Ucyclyd Pharma, 888-829-2593, FDA approved for hyperammonemia due to urea cycle defects and neonatal hyperammonemic coma) can be administered to augment nitrogen excretion. If < 20 kg, administer loading dose 250 mg/kg (2.5 mL/kg) in 10% glucose via central line over 90-120 minutes, then 250 mg/kg/d (2.5 mL/kg/d) in 10% glucose via central continuous infusion; if >20 kg, administer 5.5 g/m2 (55 mL/m2) over 90-120 minutes, then 5/5 g/m2/d (55 mL/m2/d). Ammonul must be given by central line.
- Arginine is an essential amino acid in patients with urea cycle defects and should be administered as arginine HCL (600 mg/kg, ie, 6 mL/kg, IV in 10% glucose over 90-120 minutes, then 600 mg/kg/d IV continuous infusion) unless the patient has arginase deficiency in which case it should not be given. Arginine dose should be decreased to 200 mg/kg for known carbamyl phosphate synthetase (CPS) or ornithine transcarbamylase (OTC) deficiency. Arginine can be mixed with Ammonul.
- For ammonia level greater than 500-600 mg/dL before Ammonul or greater than 300 mg/dL and rising after Ammonul, hemodialysis should likely be initiated.
- If hemodialysis is not redily available, peritoneal dialysis (< 10% as effective as hemodialysis) or double volume exchange transfusion (even less effective) can be performed while arrangements are made to transport to a center where hemodialysis is possible, as long as this does not delay transfer
- Two to three days of therapy is usually necessary.
Administer cofactors if indicated.
- L-carnitine (25-50 mg/kg IV over 2-3 minutes or as infusion, followed by 25-50 mg/kg/d maximum 3 g/d) may be administered empirically in life-threatening situations associated with primary carnitine deficiency. Administration of L-carnitine to patients with secondary carnitine deficiency is controversial. Consultation with an IEM specialist is recommended.
- Carnitine cannot be given with Ammonul.
- Pyridoxine (B6) (100 mg IV) should be given to neonates with seizures unresponsive to conventional anticonvulsants.
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|Poor feeding, vomiting, failure to thrive||X||+||++||+||X||X||+||+||+|
|Dysmorphic features and/or skeletal or organ malformations||X||X||-||-||X||X||+||X||X|
|Abnormal hair and/or dermatitis||-||X||X||-||-||-||-||-||-|
|Cardiomegaly and/or arrhythmias||-||X||-||-||X||X||+||-||X|
|Hepatosplenomegaly and/or splenomegaly||X||+||+||+||+||+||+||X||X|
|Developmental delay +/- neuroregression||+||+||+||X||X||X||++||+||+|
|Lethargy or coma||X||++||++||+||X||++||-||-||X|
|Hypotonia or hypertonia||+||+||+||+||X||+||X||+||X|
|Primary metabolic acidosis||X||++||+||+||X||+||-||-||X|
|Primary respiratory alkalosis||-||-||+||-||-||-||-||-||-|
|*Within disease categories, not all diseases have all findings. For disorders with episodic decompensation, clinical and laboratory findings may be present only during acute crisis. For progressive disorders, findings may not be present early in the course of disease.
AA = Amino acidopathy
OA = Organic acidopathy
UCD = Urea cycle defect
CD = Carbohydrate disorder
GSD = Glycogen storage disorder
FAD = Fatty acid oxidation defect
LSD = Lysosomal storage disease
PD = Peroxisomal disorder
MD = Mitochondrial disorder
++ = Always present
+ = Usually present
X = Sometimes present
- = Absent
H = Inappropriately high
L = Inappropriately low
A = Appropriate