Inborn errors of metabolism: Metabolic emergencies
- V Reid Sutton, MD
V Reid Sutton, MD
- Professor of Molecular and Human Genetics
- Baylor College of Medicine
Congenital metabolic disorders result from the absence or abnormality of an enzyme or its cofactor, leading to either accumulation or deficiency of a specific metabolite (table 1 and table 2 and table 3 and table 4 and table 5 and table 6).
The presenting features of inborn errors of metabolism (IEM) may be acute or chronic. Acute signs include episodic vomiting accompanied by dehydration or shock, lethargy and coma, rhabdomyolysis, and hypoglycemia associated with minor illnesses, stress, or a prolonged fast. Chronic signs of metabolic disease include growth delay/failure to thrive (FTT), hepatomegaly, cardiomyopathy, spastic diplegia, and developmental delay or regression.
Optimal outcome for children with IEM depends upon recognition of the signs and symptoms of metabolic disease, prompt evaluation, and referral to a center familiar with the evaluation and management of these disorders . Delay in diagnosis may result in acute metabolic decompensation, progressive neurologic injury, or death.
This topic provides an overview of the presentation, initial evaluation, and management of children with suspected IEM who present with acute metabolic decompensation. Confirmation of diagnosis of specific disorders typically requires specialized testing and should be undertaken in consultation with a specialist in genetics or metabolic diseases. Determination of the specific IEM is reviewed separately. The classification and most common chronic presentations of IEM are also discussed separately, as are individual disorders. (See "Inborn errors of metabolism: Classification" and "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features" and "Inborn errors of metabolism: Identifying the specific disorder".)
CAUSES OF ACUTE METABOLIC DECOMPENSATION
Inborn errors of metabolism (IEM) can be grouped into disorders of intermediary metabolism (classic IEM), disorders of biosynthesis and breakdown of complex molecules, and disorders of neurotransmitter metabolism (table 1). Many of the disorders of intermediary metabolism can present with acute, life-threatening illness, particularly organic acidurias, urea cycle disorders, maple syrup urine disease, and fatty acid oxidation disorders. Neurotransmitter defects and related disorders can present with severe metabolic encephalopathy. In contrast, the disorders involving complex molecules tend to progress more slowly and do not typically cause acute metabolic decompensation. (See "Inborn errors of metabolism: Classification", section on 'Classification'.)
- Champion MP. An approach to the diagnosis of inherited metabolic disease. Arch Dis Child Educ Pract Ed 2010; 95:40.
- Weiner DL. Metabolic emergencies. In: Textbook of pediatric emergency medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott, Williams and Wilkins, Philadelphia 2006. p.1193.
- Cleary MA, Green A. Developmental delay: when to suspect and how to investigate for an inborn error of metabolism. Arch Dis Child 2005; 90:1128.
- Calvo M, Artuch R, Macià E, et al. Diagnostic approach to inborn errors of metabolism in an emergency unit. Pediatr Emerg Care 2000; 16:405.
- Ficicioglu C, Bearden D. Isolated neonatal seizures: when to suspect inborn errors of metabolism. Pediatr Neurol 2011; 45:283.
- Dhamija R, Patterson MC, Wirrell EC. Epilepsy in children--when should we think neurometabolic disease? J Child Neurol 2012; 27:663.
- Gkampeta A, Pavlou E. Infantile spasms (West syndrome) in children with inborn errors of metabolism: a review of the literature. J Child Neurol 2012; 27:1295.
- Saudubray JM, Chappentier C. Clinical phenotypes: Diagnosis/algorithms. In: Metabolic and molecular bases of inherited disease, Scriver CR, Beaudet AL, Sly WS, Valle D (Eds), McGraw-Hill, New York 2001. p.1327.
- Leonard JV, Morris AA. Diagnosis and early management of inborn errors of metabolism presenting around the time of birth. Acta Paediatr 2006; 95:6.
- Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid-responsive neonatal seizures. J Child Neurol 1999; 14:529.
- Gallagher RC, Van Hove JL, Scharer G, et al. Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol 2009; 65:550.
- Bonham JR, Downing M. Metabolic deficiencies and SIDS. J Clin Pathol 1992; 45:33.
- Wappner RS. Biochemical diagnosis of genetic diseases. Pediatr Ann 1993; 22:282.
- Gibson K, Halliday JL, Kirby DM, et al. Mitochondrial oxidative phosphorylation disorders presenting in neonates: clinical manifestations and enzymatic and molecular diagnoses. Pediatrics 2008; 122:1003.
- Maestri NE, Clissold D, Brusilow SW. Neonatal onset ornithine transcarbamylase deficiency: A retrospective analysis. J Pediatr 1999; 134:268.
- Broomfield A, Grunewald S. How to use serum ammonia. Arch Dis Child Educ Pract Ed 2012; 97:72.
- Burton BK. Inborn errors of metabolism in infancy: a guide to diagnosis. Pediatrics 1998; 102:E69.
- Kronick JB, Scriver CR, Goodyer PR, Kaplan PB. A perimortem protocol for suspected genetic disease. Pediatrics 1983; 71:960.
- Poggi F, Rabier D, Vassault A, et al. [Protocol of metabolic investigations in hereditary metabolic diseases]. Arch Pediatr 1994; 1:667.
- Lindor NM, Karnes PS. Initial assessment of infants and children with suspected inborn errors of metabolism. Mayo Clin Proc 1995; 70:987.
- Roth KS. Inborn errors of metabolism: the essentials of clinical diagnosis. Clin Pediatr (Phila) 1991; 30:183.
- Chakrapani A, Cleary MA, Wraith JE. Detection of inborn errors of metabolism in the newborn. Arch Dis Child Fetal Neonatal Ed 2001; 84:F205.
- Wang HS, Kuo MF, Chou ML, et al. Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy. Arch Dis Child 2005; 90:512.
- Bagci S, Zschocke J, Hoffmann GF, et al. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2008; 93:F151.
- Barnes PM, Wheldon DB, Eggerding C, et al. Hyperammonaemia and disseminated herpes simplex infection in the neonatal period. Lancet 1982; 1:1362.
- Ogier de Baulny H. Management and emergency treatments of neonates with a suspicion of inborn errors of metabolism. Semin Neonatol 2002; 7:17.
- Ellaway CJ, Wilcken B, Christodoulou J. Clinical approach to inborn errors of metabolism presenting in the newborn period. J Paediatr Child Health 2002; 38:511.
- Nicolai J, van Kranen-Mastenbroek VH, Wevers RA, et al. Folinic acid-responsive seizures initially responsive to pyridoxine. Pediatr Neurol 2006; 34:164.
- Nasser M, Javaheri H, Fedorowicz Z, Noorani Z. Carnitine supplementation for inborn errors of metabolism. Cochrane Database Syst Rev 2012; :CD006659.
- CAUSES OF ACUTE METABOLIC DECOMPENSATION
- CLINICAL PRESENTATIONS
- Lethargy and coma
- SIDS or ALTE
- LABORATORY FINDINGS
- Acid-base disorders
- INITIAL EVALUATION
- EVALUATION OF SPECIFIC CRITICAL PRESENTATIONS
- Acid-base disorder
- SIDS and ALTE
- DIFFERENTIAL DIAGNOSIS
- IMMEDIATE MANAGEMENT
- Supportive measures
- Provision of cofactors