Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access
Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc
Journal website https://www.jofem.org

Review

Volume 11, Number 3-4, August 2021, pages 65-68


When to Consider an Inborn Error of Metabolism in Adults?

Tables

Table 1. Bayes Theorem Illustrated in an Example of Mitochondrial Disease
 
Mitochondrial disease presentMitochondrial disease absent
aExample 1: Screening for a mitochondrial disease by using serum lactate levels (sensitivity 77%, specificity 93% [14]) in a patient population presenting with fatigue (estimated prevalence of mitochondrial disease, assuming that all patients with mitochondrial disease are fatigued: 1:1,000 [15, 16]) yields an unacceptably low positive predictive value (PPV); the chance of having a mitochondrial disease with elevated serum lactate is still only 1:100. bExample 2: The use of serum lactate as a diagnostic test for mitochondrial disease in carefully selected patients (i.e., the presence of diabetes and hearing impairment [17]) yields a much better PPV; the chance of having a mitochondrial disease with elevated serum lactate is 1:3, modified after [18]. PPV: positive predictive value; NPV: negative predictive value.
Example 1a: low a priori chance
  Lactate positive8691PPV: 0.01
  Lactate negative29,291NPV: 0.99
  Sensitivity: 0.77Specificity: 0.93Prevalence: 0.001
Example 2b: high a priori chance
  Lactate positive385665PPV: 0.37
  Lactate negative1158,835NPV: 0.99
  Sensitivity: 0.77Specificity: 0.93Prevalence: 0.05

 

Table 2. General Principles That Should Be Taught in Order to Facilitate Early Diagnosis of an Inborn Error of Metabolism in Adults
 
Diagnosing an IEM is not restricted to pediatricians, some IEMs typically manifest at adult age.
Given the a low a priori chance of an IEM it is not advocated to screen for these disorders in the general population, as it will yield unacceptably high false positive rates. Instead, diagnostic tests should be reserved for selected cases.
An IEM (or another rare disease) should be considered when there is an atypical presentation of a common clinical problem (“question mark”); an IEM should be suspected when there are additional guiding signs (“plus sign”). Identification of question marks and plus signs can be stimulated by reflective reasoning.
When an IEM is suspected, the following steps can be undertaken to make the final diagnosis: 1) use (online) reference works; 2) use diagnosis support system; 3) initiate a multidisciplinary meeting; or 4) consult an expert. In this stage, exclusion of potential diagnoses because of low likelihood should be avoided.