Iron-deficiency anaemia, gastric hyperplasia, and elevated gastrin levels due to potassium channel dysfunction in the Jervell and Lange-Nielsen Syndrome.
OBJECTIVE
We investigated extra-cardiac clinical symptoms and signs in the rare Jervell and Lange-Nielsen Syndrome, characterised by impaired KCNQ1 function, a gene essential for gastric acid secretion.


METHODS
All Swedish Jervell and Lange-Nielsen cases with double KCNQ1 mutations (14 cases) were investigated by medical record review, an interview, and were offered laboratory testing for iron-deficiency anaemia and gastrointestinal markers.


RESULTS
A history of iron-deficiency anaemia in 12 of 14 patients and subjective gastrointestinal symptoms in 13 of 14 patients was revealed. Previous endoscopy in five cases had revealed no case of coeliac or inflammatory bowel disease but three cases of mucosal hyperplasia/dysplasia. Current signs of anaemia or iron substitution were present in 9 of 12 tested cases. Elevated levels of gastrin in seven of nine cases, pepsinogen in six of seven cases, and faecal calprotectin in nine of nine cases were present. A significant correlation between elevated gastrin levels and concurrent iron-deficiency and/or anaemia was revealed (p-value 0.039).


CONCLUSIONS
A high frequency of extra-cardiac clinical symptoms and previous medical investigations was found. We propose that the Jervell and Lange-Nielsen Syndrome phenotypically includes gastrointestinal symptoms/signs and secondary iron-deficiency anaemia owing to hypochlorhydria on the basis of KCNQ1 mutations. The resultant elevated gastrin level is a potential risk factor for later gastrointestinal cancer. Clinical monitoring with regard to developing anaemia and hypergastrinaemia should be considered in the Jervell and Lange-Nielsen Syndrome.
Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden. annika.winbo@pediatri.umu.se
Annika
A
Winbo
Olof
O
Sandström
Richard
R
Palmqvist
Annika
A
Rydberg
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D005773:Gastroscopy; D005838:Genotype; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007407:Interviews as Topic; D029593:Jervell-Lange Nielsen Syndrome / Q000235:genetics*; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020116:Pepsinogen A / Q000378:metabolism; D010641:Phenotype; D013270:Stomach / Q000473:pathology; D013548:Sweden
D015415:Biomarkers; D005755:Gastrins; D051657:KCNQ1 Potassium Channel; D039841:Leukocyte L1 Antigen Complex; D020116:Pepsinogen A