Medication Summary

Emergency medications for inborn errors of metabolism (IEMs) in infants and children include drugs to eliminate toxic metabolites and/or amino acids and enzyme cofactors to compensate for metabolic deficiencies. These and other drugs may be required to maintain and treat the underlying IEM. Some IEMs are treated with replacement enzymes that are FDA approved, designated as orphan drugs, or investigational.^[16]

Helpful Web sites for finding information on orphan drug designation include the following:

National Organization for Rare Disorders (NORD) (lists more than 1000 rare diseases)
United States FDA's Other Sources of Rare Disease/Orphan Product Information (list of Web sites that provide information on rare diseases and orphan drugs)
United States FDA's List of Orphan Drug Designations and Approvals

Class Summary

Treatment of hyperammonemia; enhances elimination of nitrogen. This drug is FDA approved for treatment of hyperammonemia due to urea cycle defects and is available only from a specialty wholesaler, Ucyclyd Pharma (888-829-2593). For more information, see Ammonul prescribing information.

Sodium phenylacetate and sodium benzoate (Ammonul)

View full drug information

Indicated for acute hyperammonemic and associated encephalopathy due to urea cycle defects. For ammonia levels >500-600 mcg/dL, hemodialysis is the preferred treatment; however, sodium phenylacetate and sodium benzoate should be considered if dialysis cannot be initiated immediately. Benzoate combines with glycine to form hippurate, which is excreted in urine. One mol of benzoate removes 1 mol of nitrogen. Phenylacetate conjugates (via acetylation) glutamine in the liver and kidneys to form phenylacetylglutamine, which is excreted by the kidneys. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (2 mol of nitrogen). Ammonul should be administered with arginine-HCL for carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or argininosuccinate lyase (ASL) deficiencies and should not be given for arginase deficiency. Approved as adjunctive treatment of acute hyperammonemia associated with encephalopathy caused by urea cycle enzyme deficiencies. Preparation contains 100 mg/mL each of sodium phenylacetate and sodium benzoate and comes in 50-mL vials. Must dilute IV dose in at least 25 mL/kg of dextrose 10% up to 600 mL. Do not mix directly with other medications, but it may be piggybacked. Give in addition to daily fluid requirement but decrease maintenance fluid by volume of Ammonul given.

Class Summary

Essential amino acid used for certain urea cycle defects.

Arginine (R-Gene)

View full drug information

Enhances production of ornithine, which facilitates incorporation of waste nitrogen into the formation of citrulline and argininosuccinate. Provides 1 mol of urea plus 1 mol ornithine per mol of arginine when cleaved by arginase. Preparation is 10% arginine hydrochloride. Can be mixed with sodium phenylacetate and sodium benzoate. If administering separately, mix with sodium bicarbonate.

Class Summary

Enzyme cofactors are used to enhance the activity of cofactor-dependent enzymes.

Pyridoxine

View full drug information

Precursor of pyridoxal, which functions in the metabolism of proteins, carbohydrates, and fats. Also aids in the release of liver- and muscle-stored glycogen and in the synthesis of GABA (within the CNS) and heme. Involved in synthesis of GABA within the CNS. Indicated for seizures of unknown etiology unresponsive to conventional anticonvulsants and for seizures in patients with known pyridoxine-dependent IEM. Give undiluted or mix with other solutions. Incompatible with alkaline or oxidizing solutions and iron salts. Not to be mixed with sodium bicarbonate.

Class Summary

This agent is used for the treatment of primary and secondary carnitine deficiency.

Levocarnitine (Carnitor)

View full drug information

An amino acid derivative, synthesized from methionine and lysine, required in energy metabolism. Can promote excretion of excess fatty acids in patients with defects that bioaccumulate acyl-CoA esters. Carnitine is indicated for most organic acidemias and is controversial for fatty acid oxidation defects.

Mak CM, Lee HC, Chan AY, Lam CW. Inborn errors of metabolism and expanded newborn screening: review and update. Crit Rev Clin Lab Sci. 2013 Nov. 50 (6):142-62. [QxMD MEDLINE Link].
Newborn Screening. National Newborn Screening and Genetics Resource Center. Available at http://genes-r-us.uthscsa.edu/resources/consumer/statemap.htm. November 3, 2014; Accessed: September 5, 2017.
Garcia-Cazorla A, Duarte ST. Parkinsonism and inborn errors of metabolism. J Inherit Metab Dis. 2014 Jul. 37 (4):627-42. [QxMD MEDLINE Link].
Newborn Screening Act Sheet and Confirmatory Algorithms. American College of Medical Genetics and Genomics. Available at https://www.acmg.net/ACMG/Publications/ACT_Sheets_and_Confirmatory_Algorithms/NBS_ACT_Sheets_and_Algorithm_Table/ACMG/Publications/ACT_Sheets_and_Confirmatory_Algorithms/NBS_ACT_Sheets_and_Algorithms_Table.aspx?hkey=e2c16055-8cdc-4b22-a53b-b863622007c0. Accessed: September 5, 2017.
Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY. Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning. Mol Genet Metab. 2014 Sep-Oct. 113 (1-2):14-26. [QxMD MEDLINE Link]. [Full Text].
Argmann CA, Houten SM, Zhu J, Schadt EE. A Next Generation Multiscale View of Inborn Errors of Metabolism. Cell Metab. 2016 Jan 12. 23 (1):13-26. [QxMD MEDLINE Link]. [Full Text].
Leach EL, Shevell M, Bowden K, Stockler-Ipsiroglu S, van Karnebeek CD. Treatable inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review. Orphanet J Rare Dis. 2014 Nov 30. 9:197. [QxMD MEDLINE Link]. [Full Text].
Vairo FP, Boczek NJ, Cousin MA, Kaiwar C, Blackburn PR, Conboy E, et al. The prevalence of diseases caused by lysosome-related genes in a cohort of undiagnosed patients. Mol Genet Metab Rep. 2017 Dec. 13:46-51. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Waisbren SE. Expanded newborn screening: information and resources for the family physician. Am Fam Physician. 2008 Apr 1. 77(7):987-94. [QxMD MEDLINE Link]. [Full Text].
Byers SL, Ficicioglu C. Infant with cardiomyopathy: When to suspect inborn errors of metabolism?. World J Cardiol. 2014 Nov 26. 6(11):1149-55. [QxMD MEDLINE Link]. [Full Text].
van Karnebeek CD, Shevell M, Zschocke J, Moeschler JB, Stockler S. The metabolic evaluation of the child with an intellectual developmental disorder: diagnostic algorithm for identification of treatable causes and new digital resource. Mol Genet Metab. 2014 Apr. 111 (4):428-38. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Illsinger S, Das AM. Impact of selected inborn errors of metabolism on prenatal and neonatal development. IUBMB Life. 2010 Jun. 62(6):403-13. [QxMD MEDLINE Link].
Weiner DL. Inborn errors of metabolism. Aghababian RV, ed. Emergency medicine: the core curriculum. Philadelphia: Lippincott-Raven; 1999. 707.
Dickson PI, Tolar J. The individual (single patient) IND for inborn errors of metabolism. Mol Genet Metab. 2014 Oct 13. [QxMD MEDLINE Link].
Acute Illness Protocols. New England Consortium of Metabolic Programs at Children's Hospital Boston. Available at http://newenglandconsortium.org/for-professionals/acute-illness-protocols/. September 16, 2013; Accessed: September 5, 2017.

Media Gallery

of 0

Table 1. Clinical and Laboratory Findings of Inborn Errors of Metabolism

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

Back to List

Inborn Errors of Metabolism Medication

Medication Summary

Ammonium Detoxicants

Class Summary

Sodium phenylacetate and sodium benzoate (Ammonul)

Sodium phenylacetate and sodium benzoate (Ammonul)

Amino Acid