Testing for lactase non-persistence in a Dutch population: Genotyping versus the hydrogen breath test.

BACKGROUND: Lactose intolerance is defined as the presence of gastrointestinal symptoms, such as bloating, abdominal pain or diarrhoea, after consumption of lactose in individuals with lactose malabsorption. Most cases involve primary lactose intolerance, caused by a loss of activity of the enzyme lactase, needed for digestion of lactose. A traditional method of establishing lactose intolerance is the hydrogen breath test (HBT), accompanied by a questionnaire to document complaints experienced by the patient during the test. Due to knowledge on lactase-persistent alleles, DNA genotyping has become available for the diagnostic work-up for lactose intolerance. Both methods are currently in use. The aim of this study is to provide a definite diagnostic approach for patients suspected of lactose intolerance in a Dutch population. METHODS: In this retrospective, observational study, patients aged 15 years or older were included after presenting to their treating physician with symptoms suggestive of lactose intolerance. HBT, including a questionnaire to document complaints and DNA genotyping of LCT-13,910 C/T was performed for each patient as part of a routine diagnostic work-up. RESULTS: 1101 patients were included (29% men). Positive and negative predictive value, sensitivity and specificity of HBT versus DNA genotyping were 80% (CI 75-84), 97% (CI 96-98), 89% (CI 84-92) and 94% (92-96) respectively. The use of the questionnaire added little diagnostic value. CONCLUSIONS: In a population with a high prevalence of lactase-persistent alleles, we advise to exclude HBT from the diagnostic route for suspected lactose intolerance, and replace it with genotyping of lactase-persistent alleles.

Extreme elevation of serum angiotensin-converting enzyme (ACE) activity: always consider familial ACE hyperactivity.

Measurement of serum angiotensin-converting enzyme (ACE) activity can be helpful in the diagnosis and disease monitoring of sarcoidosis. Elevated serum ACE activity is found in 60-70% of sarcoidosis patients. Usually, the ACE activity is mildly increased (<3-fold the upper limit of the reference range) in sarcoidosis patients. Extremely elevated ACE activity is suggestive of the benign condition known as 'familial hyperactivity of ACE'. Familial hyperactivity of ACE is a relatively rare condition and can be confirmed by genetic testing. Considering a genetic cause of strongly elevated serum ACE activity is important to prevent possible overdiagnostics. Here, we highlight the factors that may complicate the interpretation of serum ACE activity measurements, and we present two cases that illustrate the importance of interdisciplinary consultation when extremely elevated serum ACE activity is measured.

Introduction of a new cobalamin (vitamin B12) assay: lessons from a flawed validation study.

BACKGROUND: Plasma vitamin B12 [cobalamin (Cbl)] concentrations are usually measured as a screening marker for vitamin B12 deficiency. Siemens Healthcare Diagnostics has introduced Cbl assays for various platforms, i.e., the immulite (IML) 2000 and 2500. In our laboratories, regular validation studies for the IML 2500 were conducted and showed acceptable quality specifications. After the introduction of the IML 2500 Cbl assay, clinicians in the department of internal medicine reported an increased frequency of patients with Cbl-concentrations less than 148 pmol/L. METHODS: In order to investigate this claim from the clinicians, we retrospectively analyzed the internal and external quality control (QC) of the Cbl assay. In addition, the monthly patient means for the Cbl assay were analyzed both before and after the introduction of the new Cbl assay. RESULTS: No abnormalities were found in the internal and external QCs. However, the monthly patient means for the Cbl assay showed a statistically significant decrease in cobalamin concentrations. Siemens acknowledged the problems and formulated a new Cbl assay, which was subsequently validated in our laboratories and showed equivocal Cbl results when compared to the IML 2000 Cbl assay. CONCLUSIONS: We report a flawed validation study conducted by the manufacturer that resulted in an undetected analytical problem in the IML 2500 Cbl assay, its subsequent introduction on the market, the final recognition of the poor performance of the assay by our clinicians, and the eventual resolution by the manufacturer. Hence, it emphasizes the utmost importance for thorough comparison between assays over the entire measurement range, even when both assays are produced by the same manufacturer.