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Inborn Errors of Metabolism Treatment & Management

  • Author: Debra L Weiner, MD, PhD; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Feb 18, 2015
 

Prehospital Care

Access and establish airway, breathing, circulation.

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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).[6] 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.[2]

Emergent treatment

See the following steps:[6]

  • 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.[6]
    • 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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Consultations

Consider consultation with an IEM specialist.[7]

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Contributor Information and Disclosures
Author

Debra L Weiner, MD, PhD Attending Physician, Division of Emergency Medicine, Children's Hospital, Boston; Assistant Professor, Department of Pediatrics, Harvard Medical School

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Wayne Wolfram, MD, MPH Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center; Chairman, Pediatric Institutional Review Board, Mercy St Vincent Medical Center, Toledo, Ohio

Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Garry Wilkes, MBBS, FACEM Director of Clinical Training (Simulation), Fiona Stanley Hospital; Clinical Associate Professor, University of Western Australia; Adjunct Associate Professor, Edith Cowan University, Western Australia

Disclosure: Nothing to disclose.

References
  1. Huang X Dr, Yang L Dr, Tong F Dr, Yang R Dr, Zhao Z Prof. Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China. BMC Pediatr. 2012 Feb 24. 12(1):18. [Medline].

  2. Newborn Screening Status Report. Updated March 11, 2009. National Newborn Screening and Genetics Resource Center. Available at http://genes-r-us.uthscsa.edu/nbsdisorders.pdf.

  3. Waisbren SE. Expanded newborn screening: information and resources for the family physician. Am Fam Physician. 2008 Apr 1. 77(7):987-94. [Medline]. [Full Text].

  4. Byers SL, Ficicioglu C. Infant with cardiomyopathy: When to suspect inborn errors of metabolism?. World J Cardiol. 2014 Nov 26. 6(11):1149-55. [Medline]. [Full Text].

  5. ACGME Newborn Screening Work Group: Levy HL, Watson, MS, Metabolic Disorders: Berry G, Goodman S, Marsden D, et al. Newborn Screening Act Sheet and Confirmatory Algorithms. Newborn Screening ACT Sheets and Confirmatory Algorithms. Available at http://www.acmg.net/resources/policies/ACT/condition-analyte-links.htm. Accessed: 1/30/09.

  6. Weiner DL. Inborn errors of metabolism. Aghababian RV, ed. Emergency medicine: the core curriculum. Philadelphia: Lippincott-Raven; 1999. 707.

  7. Stockler S, Moeslinger D, Herle M, Wimmer B, Ipsiroglu OS. Cultural aspects in the management of inborn errors of metabolism. J Inherit Metab Dis. 2012 Feb 23. [Medline].

  8. Dickson PI, Tolar J. The individual (single patient) IND for inborn errors of metabolism. Mol Genet Metab. 2014 Oct 13. [Medline].

  9. Illsinger S, Das AM. Impact of selected inborn errors of metabolism on prenatal and neonatal development. IUBMB Life. 2010 Jun. 62(6):403-13. [Medline].

  10. Acute Illness Protocols. New England Consortium of Metabolic Programs at Children's Hospital Boston. Available at http://www.childrenshospital.org/newenglandconsortium/NBS/Emergency_Protocols.html. Accessed: 1/30/09.

  11. Arn PH, Valle DL, Brusilow SW. Inborn errors of metabolism: not rare, not hopeless. Contemp Pediatr. 1988. 5:47-63.

  12. Burton BK. Inborn errors of metabolism in infancy: a guide to diagnosis. Pediatrics. 1998 Dec. 102(6):E69. [Medline].

  13. Calvo M, Artuch R, Macia E, et al. Diagnostic approach to inborn errors of metabolism in an emergency unit. Pediatr Emerg Care. 2000 Dec. 16(6):405-8. [Medline].

  14. Chace DH, Kalas TA, Naylor EW. Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem. 2003 Nov. 49(11):1797-817. [Medline].

  15. Chow SL, Gandhi V, Krywawych S, Clayton PT, Leonard JV, Morris AA. The significance of a high plasma ammonia value. Arch Dis Child. 2004 Jun. 89(6):585-6. [Medline].

  16. Enns GM, Packman S. Diagnosing inborn errors of metabolism in the newborn: clinical features. Neo Reviews. 2001. 2000:e183-90.

  17. Fernandes J, Saudubray JM, Van den Berghe G. Inborn Metabolic Diseases: Diagnosis and Treatment. 3rd ed. Springer-Verlag: 2000.

  18. Funded by NIH. PI: Pagon RA. GeneReviews, Laboratory Directory, Clinic Directory, Educational Materials. GeneTests. Available at http://bit.ly/eOUcdy. Accessed: 1/30/09.

  19. Garganta CL, Smith WE. Metabolic evaluation of the sick neonate. Semin Perinatol. 2005 Jun. 29(3):164-72. [Medline].

  20. Goodman SI. Inherited metabolic disease in the newborn: approach to diagnosis and treatment. Adv Pediatr. 1986. 33:197-223. [Medline].

  21. Hoffman GF, Nyhan WL, Zschocke J. Inherited Metabolic Diseases. Philadelphia: Lippincott Williams & Wilkins; 2002.

  22. James PM, Levy HL. The clinical aspects of newborn screening: importance of newborn screening follow-up. Ment Retard Dev Disabil Res Rev. 2006. 12(4):246-54. [Medline].

  23. Kwon KT, Tsai VW. Metabolic emergencies. Emerg Med Clin North Am. 2007 Nov. 25(4):1041-60, vi. [Medline].

  24. Marsden D, Larson C, Levy HL. Newborn screening for metabolic disorders. J Pediatr. 2006 May. 148(5):577-584. [Medline].

  25. McKusik VA. OMIM Online Mendelian Inheritance in Man [database online]. McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). Available at http://www.ncbi.nlm.nih.gov/omim.

  26. Nasser M, Javaheri H, Fedorowicz Z, Noorani Z. Carnitine supplementation for inborn errors of metabolism. Cochrane Database Syst Rev. 2012 Feb 15. 2:CD006659. [Medline].

  27. Ward JC. Inborn errors of metabolism of acute onset in infancy. Pediatr Rev. 1990 Jan. 11(7):205-16. [Medline].

  28. Weinstein DA, Butte AJ, Raymond K. High incidence of unrecognized metabolic and endocrinologic disorders in acutely ill children with previously unrecognized hypoglycemia. Pediatr Res. 2001. 49:103A#578.

 
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Table 1. Clinical and Laboratory Findings of Inborn Errors of Metabolism
Clinical Findings* AA OA UCD CD GSD FAD LSD PD MD
Episodic decompensation X + ++ + X + - - X
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
Seizures X X + X X X + + X
Hypotonia or hypertonia + + + + X + X + X
Ataxia - X + X - X X - -
Abnormal odor X + X - - - - - -
Laboratory Findings*                  
Primary metabolic acidosis X ++ + + X + - - X
Primary respiratory alkalosis - - + - - - - - -
Hyperammonemia X + ++ X - + - - X
Hypoglycemia X X - + X + - - X
Liver dysfunction X X X + X + X X X
Reducing substances X - - + - - - - -
Ketones A H A A L/A L A A H/A
*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



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