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The crucial recognition that an Inborn Error of Metabolism (IEM) is at play often comes from a nongeneticist practitioner. Rather than serve as a textbook of the many biochemical pathways affected in IEMs, this section is intended as a general and practical overview to facilitate the initial recognition and early management of a suspected metabolic crisis and provide an introduction to the most common diagnostic and management strategies. The detailed diagnosis of IEMs, interpretation of complex biochemical labs, and the nuanced management of these patients is the purview of the specialist and therefore this section cannot replace timely consultation with a specialist should such a situation arise. Biochemical genetics is a subfield of Medical Genetics and physicians who specialize in this field are available around the world. Because of the rarity of IEMs, involvement of this type of specialist is often inevitable for diagnosis and management. Illnesses caused by IEMs that present more subtly (e.g., as developmental delay) are discussed in Chapter 5.

Key Point

Most symptomatic patients with inherited metabolic diseases will first present to a pediatrician, neonatologist, or emergency medicine physician.

Key Point

Essential labs whenever a metabolic disorder is suspected:

  • Complete metabolic panel (Na, K, Cl, CO2, BUN, creatinine, glucose, AST, ALT, alkaline phosphatase and/or GGT, direct/indirect bilirubin, protein, albumin, Ca, Mg, Phos)

  • Urinalysis (glucose, ketones, nitrite, leukocyte esterase, pH)

  • Blood gas (capillary or venous is acceptable)

  • Creatine kinase (noncardiac isoform)

  • Ammonia

  • Lactate

Strongly consider:

  • CBC with differential

  • Homocysteine


Table 4-1 provides a simplified association between diseases and metabolic findings that can present in crisis. Symptoms of an acute metabolic crisis often include a combination of altered mental status, seizures, organ dysfunction (particularly liver), rhabdomyolysis, or heart failure (potentially involving cardiomyopathy). Signs can include altered respiration (either tachypnea or bradypnea), an unusual odor, hepatomegaly, abnormal behavior or even psychotic symptoms, jaundice and other evidence of acute liver disease. Abnormalities detectable on routine laboratory studies can include acidosis (typically with an anion gap), hyperammonemia, elevated blood lactate, hypo- or hyperglycemia, or other electrolyte disturbances. Abnormalities in sodium and potassium may point to adrenal or other endocrine dysfunction. The challenge for the practitioner first is to consider a metabolic disturbance in the differential diagnosis, and then to identify which signs, symptoms, and laboratory studies support this conclusion to guide initial management. While it may seem preferable to delay sending advanced metabolic studies until a specialist can consult, the practitioner should be familiar with and comfortable sending advanced metabolic screens because delaying testing delays a diagnosis. Test interpretation should be done in consultation with a qualified geneticist, but the testing itself need not be postponed for a specialist.

Table 4-1.Presenting findings during metabolic crisis and some associated diseases.

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