Inborn errors of metabolism: an emergency medicine approach

Correspondence/ American Journal of Emergency Medicine 34 (2016) 307337 317

antipsychotic drugs were encountered, with the most common being quetiapine. The rate of coingestion in patients given AC (40%) was not significantly different from the rate seen in those patients who did not receive AC (37.5%, P = .425).

The median time from toxic ingestion to EMS arrival for patients who did receive AC was 27.1 minutes (interquartile range [IQR], 19.3- 37.3 minutes; range, 8-120 minutes) and 36.6 minutes (IQR, 21.0-60.6 minutes; range, 6-120 minutes) for patients who did not receive AC (P = .1416). The median total EMS encounter time for patients who re- ceived AC was 26.8 minutes (IQR, 28.6-39.8 minutes; range, 10-53 mi- nutes), and the median total EMS encounter time was 25.6 minutes (IQR, 22.5-29.8 minutes; range, 10-39 minutes) for those who did not receive AC (P = .4715). The median Ambulance transport time for pa- tients who received AC was 13.6 minutes (IQR, 9.3-17.4 minutes; range, 1-42 minutes), compared with a median transport time of 12.0 minutes (IQR, 9.8-15.7 minutes; range, 1-25 minutes) for patients who did not receive AC (P = .8650).

Complications were seen in one of the patients who did not receive AC (4.2%), whereas 2 patients who received AC experienced complica- tions (6.7%). There was no significant difference in the rate of complica- tions between groups (P = .689). There was also 1 case of emesis among patients who did not receive AC (4.2%), compared with 3 cases (10%) among those who did receive AC (P = .418).

Limitations of our review include its retrospective design, our reli- ance on documentation as recorded by paramedics, our inability to track patient outcomes after arrival in the ED, our inability to confirm in- gestion of the alleged antipsychotic medication, and the difficulty in concluding whether the complications defined and identified in our cases were caused by AC administration or resulted from the overdose itself. However, these present data seem to be consistent with our pre- vious study suggesting that prehospital AC administration may not delay transport times of overdose patients.

Joseph Villarreal, MD

UCSD Department of Emergency Medicine, San Diego, CA

Christopher A. Kahn, MD UCSD Department of Emergency Medicine, San Diego, CA UCSD Division of Emergency Medical Services, San Diego, CA

James V. Dunford, MD UCSD Department of Emergency Medicine, San Diego, CA UCSD Division of Emergency Medical Services, San Diego, CA San Diego Fire-Rescue Department, San Diego, CA

Edward M. Castillo, PhD

UCSD Department of Emergency Medicine, San Diego, CA

Richard F. Clark, MD UCSD Department of Emergency Medicine, San Diego, CA UCSD Division of Medical Toxicology, San Diego, CA Corresponding author. 200 W. Arbor Dr

San Diego, CA, 92103

E-mail address: [email protected]


[1] Villarreal J, Kahn CA, Dunford JV, Patel E, Clark RF. A retrospective review of the Prehospital use of activated charcoal. Am J Emerg Med 2015;33(1):56-9 [Epub 2014 Oct 22].

Inborn errors of metabolism: an emergency medicine approach?,??,?

To the Editor,

Recognizing and managing metabolic emergencies due to inborn errors of metabolism (IEM) can be challenging to emergency physicians. Inborn errors of metabolism present similarly to systemic Pathologic conditions and are less common than many other conditions (up to 1 in 800 to 1 in 2500 live births) [1,2], such as sepsis and congenital heart disease. Infants with IEM may have a normal birth and an uneventful period for days to years before manifestation of symptoms. These symptoms are variable in nature and nonspecific, placing a great deal of importance on a thorough yet efficient utilization of labo- ratory tests. Early suspicion, recognition, and initiation of treatment are key to stabilizing these patients and preventing Disease progression. Presentations for IEM can be divided into early and late presenta- tions. In both, manifestations are broad and may include almost every organ system. Neurologic and gastrointestinal manifestations are the most frequent [3]. The major common symptoms of IEM are presented

in Table 1.

Clinical manifestations of the neonatal time period often occur be- tween 3 days and 1 week of life. These early presentations correlate with a complete block of the metabolic pathway or complete absence of an enzyme [4,5,8-10]. These neonates often present with vomiting, tachypnea, gasping, altered mental status, lethargy, and hypothermia [3,6]. More than 90% of patients presenting in this period have neurologic symptoms and/or vomiting [10]. This vomiting in patients with IEM is due to intolerance of a toxic metabolite [7].

Inborn errors of metabolism can also present years later. These later presentations correlate with an incomplete block or absence of a protein/cofactor [4,5,8]. These patients often deteriorate in the setting of an acute stressor, such as infection [6].

An IEM should be considered in any previously healthy neonate with acute clinical decompensation. Although the differential diagnosis of IEM is broad, “THE MISFITS” mnemonic can help ensure that all life- threatening etiologies are addressed [5,9-16].

  • Trauma/Tumor (nonaccidental and accidental)
  • Heart disease/Hypovolemia/Hypoxia
  • Endocrine (congenital adrenal hyperplasia, thyrotoxicosis)
  • Metabolic (electrolyte imbalance)
  • Inborn errors of metabolism
  • Sepsis (meningitis, pneumonia, or urinary tract infection)
  • Formula mistakes (under or overdilution)
  • Intestinal (volvulus, pyloric stenosis, intussusceptions, or necrotizing enterocolitis)
  • Toxins
  • Seizures

Although these conditions must be considered, they are not exclusive of one another. For example, the presence of an infection does not rule out a concordant IEM, as patients with IEM may deterio- rate quickly and become septic [5].

When taking the history, there are several factors that help differentiate IEM from each of the other categories of “THE MISFITS”

? This manuscript did not use any grants, and it has not been presented in abstract form.

?? Conflicts of interest: None.

? This correspondence has not been published, it is not under consideration for

publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright holder.

318 Correspondence/ American Journal of Emergency Medicine 34 (2016) 307337

Table 1

Common symptoms of IEM [4-7]

Gastrointestinal Persistent or recurrent vomiting Poor feeding

failure to thrive

Hepatomegaly and/or splenomegaly Jaundice

Neurologic Altered mental status

Encephalopathy Lethargy

Poor tone Jitteriness Intractable seizures

Other Tachypnea


Unusual or musty odor Hypothermia

Table 2

Factors in the history suspicious for IEM [7]

Symptoms that worsen or emerge in a normally self-limited illness Recurrent vomiting despise multiple formula changes

Symptoms that occur when an infant switches from breast milk to cow’s milk Symptoms that begin with a new food

Family history of metabolic disease History of an unexplained infant death History of consanguinity

Table 3

Initial laboratory tests to order for suspected IEM [6]

blood glucose level venous blood gas Electrolytes

Complete blood count Renal function panel Urine dipstick Ammonia level Ketones


Liver function tests

classification. These factors are listed in Table 2. Any of these factors push the suspicion toward an IEM.

Ordering a concise set of laboratory values is vital when considering IEM. Laboratory values will differ based on the type of IEM. Inborn errors of metabolism of acute onset can be divided into those with hyperammonemia and those with metabolic acidosis. Another group is those with hypoglycemia, which may be present either with or with- out metabolic acidosis [4]. Early evaluation for hypoglycemia is essen- tial, as early brain damage can occur. Along with the Serum glucose level, important initial laboratory tests to order include a venous blood gas, electrolytes, complete blood count, a renal function panel, urine dipstick, an ammonia level, ketones, lactate, and liver functions tests [6]. These laboratory tests are listed in Table 3. In the sick neonate, an electrocardiogram, chest x-ray, blood cultures, and lumbar puncture should also be obtained [8,9,15].

immediate intervention is essential in patients with acute presenta- tions from IEM, as this may prevent severe mental and physical debility and death. The initial treatment is the same as any for an unstable infant or adult: begin with the ABCs. Next, 4 major goals of treatment should be addressed [4,11-16]:

  1. Stop metabolism of the toxin: the patient should be made NPO to remove sources of protein.
  2. Stop the process of catabolism: give dextrose 10% (D10) with 0.25 normal saline at 1.5 x maintenance fluid infusion.
  3. Remove the toxin and metabolites: medications used to treat

hyperammonemia include sodium phenyl acetate or sodium

benzoate [6]. Dialysis may be used to help remove the toxin. In pa- tients with hyperammonemia or patients who are critically ill, hemo- dialysis is the preferred method for the removal of ammonia [16].

  1. While managing IEM, any concurrent etiologies of decompensation using “THE MISFITS” should be considered and treated. Empiric anti- microbials are warranted for these patients based on hospital antibiograms and resistance patterns.

After initial stabilization, consultations are vital to manage and work-up the patient for an IEM. The pediatric intensive care unit, genetics and/or metabolism, and nephrology should be consulted for further assistance [6].


No grants or funds for research were used.

Drew Long, BS Vanderbilt University School of Medicine, Nashville, TN 37232 E-mail address: d[email protected]

Brit Long, MD*

Department of Emergency Medicine San Antonio Military Medical Center, Houston, TX 78234

E-mail address: [email protected]

*Corresponding author. 477 Perch Horizon, San Antonio

TX 78253. Tel.: +1 719 339 5510

Alex Koyfman, MD

Department of Emergency Medicine The University of Texas Southwestern Medical Center, Dallas, TX 75390

E-mail address: a[email protected]


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