There is increasing interest in sweat testing due to the recognition of genetic mutations of cystic fibrosis (CF) with borderline or even normal chloride levels in sweat. This makes the accuracy of reported data on false-positive or negative sweat tests in the literature equally important.

Most medical textbooks cite several diseases that cause abnormally high-sweat electrolytes, including glucose-6-phosphate-1-dehydrogenase (G6PD) deficiency.1 2 A defect in G6PD is the cause of a chronic non-spherocytic haemolytic anemia and is associated with high risk in malaria-endemic regions (ie, Africa), although essentially being asymptomatic in the steady state. In sporadic cases a more severe phenotype is observed. This enzyme deficiency should not be confused with glucose-6-phosphatase (EC 3.1.3.9. G6Pase) deficiency, which is the basic defect in glycogen storage disease type 1a. In this disease state, elevation of sweat electrolytes, mainly in boys, was reported previously.3

For G6PD deficiency we were, however, unable to identify any original reference in the medical literature (searching in NCBI's PubMed, Omim, and others). Consequently, we carried out sweat tests by classic pilocarpine iontophoresis with chloride and sodium determinations (Gibson and Cook method with collection of sweat into gauze and determination of chloride by coulometry and sodium by flame photometry) in eight patients with G6PD deficiency (median age 9.2 years, range 1.9–48.5, two females), and by sweat test conductivity measurements (Nanoduct® technology) in another three patients (median age 6.2 years, range 1.9–40.5, one female). The diagnosis of G6PD deficiency was made by routine laboratory test (enzymatically in blood). The mean (SD) sweat chloride level was 18.8 (9.6 mmol/l), the mean (SD) sodium level was 26.0 (10.0 mmol/l), respectively, the mean (SD) amount of sweat collected was 0.311 (0.06 g) (see also table 1). In every patient, sweat of the right and left arm was collected. The table shows the mean value of the two collections per patient. Accordingly, the result for mean (SD) conductivity was 34.3 (6.5 mmol/l). All these results fulfil international criteria for normal electrolyte and conductivity values of sweat.4 5 In subject no. 3 of the controls, the mean chloride was 44 mmol/l. This represents a borderline value, but the subject had no clinical signs of CF.

The reason for alleged false-positive sweat test in patients with G6PD deficiency is not known. Tracking back the references in the literature for the source of a report on elevated sweat electrolytes in patients with G6PD deficiency reveals that, over the years, various tables of putative false-positive sweat tests in several disease states appear to have been directly “copied and pasted” from one paper or textbook to another, a phenomenon called “chain citation”.

It seems that false-positive sweat test results for G6PD deficiency were first reported by the Committee for a Study for Evaluation of Sweat Testing for Cystic Fibrosis in 1979 as a consequence of “GAP” Conference Reports of the Cystic Fibrosis Foundation held at the Hilton Head in South Carolina, 1975.6 Since then, a large number of conditions other than CF are reported to be associated with raised sweat electrolytes. In addition to G6PD deficiency these conditions include adrenal insufficiency, familial hypoparathyroidism, nephrogenic diabetes insipidus, Mauriac's syndrome, familial cholestatic syndrome, anorexia nervosa and severe malnutrition, atopic dermatitis, KID syndrome, fucosidose, pseudohypoaldosteronism, in patients undergoing prostaglandin infusions, ectodermal dyplasia, hypothyroidism and nephrosis. In some of these diseases accurate references in peer-reviewed publications are available, and for some diseases they are lacking, such as for G6PD deficiency, ectodermal dyplasia, hypothyroidism and nephrosis (see Box 1). G6PD deficiency as a disease associated with elevated sweat electrolyte concentration appears in the review published by VA LeGrys7 who refers to the approved guideline from the National Committee for Clinical Laboratory Standards (NCCLS). However, this guideline has never been published in a peer-reviewed form.8

In conclusion and taking into account our study results, we suggest that the source of various statements for clinical and diagnostic purposes, should always be clear. As we report here in relation to glucose-6-phosphate-1-dehydrogenase deficiency, there are risks of unintentional “chain citation” which can be avoided if the original papers are consulted.