A Urinary Radioisotope‐Binding Assay to Diagnose Gräsbeck‐Imerslund Disease

Abstract

Background:Gräsbeck‐Imerslund disease (congenital familial selective vitamin B 12‐malabsorption with proteinuria, MGA1, MIM No. 261100) is a rare disorder displaying autosomal recessive inheritance. This study was designed to investigate the usefulness of measuring the activity of the urinary receptor for the intrinsic factor‐cobalamin complex as a tool to diagnose this disease.Methods:The receptor activity was measured by a radioisotope‐binding assay, using phenyl‐Sepharose gel as the adsorbant solid phase of the receptor.Results:In 10 Finnish patients, urinary receptor activity was on the average 640 times (15‐1400 times) lower than that in 13 healthy control subjects: mean values of 0.1 nmol/mol (range, 0.01‐0.32 nmol/mol) and 6.4 nmol/mol (range, 3.8‐12.4 nmol/mol) creatinine, respectively. The mean value of urinary receptor activity in 11 first‐degree, healthy relatives of the patients was 4.6 nmol/mol (range, 1.1‐10.4 nmol/mol) creatinine, a difference from levels in control subjects that is not statistically significant. When the first‐degree relatives were divided into heterozygotes (parents and siblings heterozygous for the haplotype of genetic markers associated with the disease gene) and wild‐type homozygotes (siblings not displaying the disease haplotype), no difference was seen.Conclusion:Determination of receptor activity in the urine is a highly accurate method for diagnosis of Gräsbeck‐Imerslund disease at an early stage, but it does not detect carriers of the disorder.