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Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features

V Reid Sutton, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


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). Most of these disorders are transmitted as autosomal recessive traits.

The possibility of an inborn error of metabolism (IEM) should be considered in infants, children, and adults who present with any of the clinical or laboratory features discussed below or in the topic review on metabolic emergencies, particularly if the findings remain unexplained after standard evaluation [1-6]. (See "Inborn errors of metabolism: Metabolic emergencies" and 'Age at presentation' below.)

Optimal outcome for children with IEM depends upon early recognition of the signs and symptoms of metabolic disease and prompt evaluation and referral to a center familiar with the management of these disorders [7]. Delay in diagnosis may result in acute metabolic decompensation, progressive neurologic injury, or death.

The epidemiology, pathogenesis, and most common chronic clinical and laboratory manifestations of IEM are discussed below. The presentation, initial diagnosis, and management of IEM presenting as metabolic emergencies are discussed in detail separately. The major classes of IEM and their characteristic clinical and biochemical features are described elsewhere, as is a diagnostic approach to identifying the specific IEM. In addition, many of the individual disorders are covered in separate topic reviews (see specific topic reviews). (See "Inborn errors of metabolism: Metabolic emergencies" and "Inborn errors of metabolism: Classification" and "Inborn errors of metabolism: Identifying the specific disorder".)


Individual IEM are rare disorders, most having an incidence of less than 1 per 100,000 births. However, when considered collectively, the incidence may approach 1 in 800 to 1 in 2500 births [8,9]. In one review of cases of IEM diagnosed in British Columbia (a predominantly Caucasian population) between 1969 and 1996, estimates of incidence of various classes of disorders were as follows:

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Literature review current through: Nov 2017. | This topic last updated: Sep 08, 2017.
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