A urinary radioisotope-binding assay to diagnose Gräsbeck-Imerslund disease.
BACKGROUND
Gräsbeck-Imerslund disease (congenital familial selective vitamin B12-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.


CONCLUSIONS
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.
Dugué
B
B
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Aminoff
M
M
Aimone-Gastin
I
I
Leppänen
E
E
Gräsbeck
R
R
Guéant
J L
JL
D000042:Absorption; D000328:Adult; D000368:Aged; D000749:Anemia, Megaloblastic / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D005387:Finland; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D011507:Proteinuria / Q000235:genetics; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis*; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000235:genetics* / Q000652:urine
D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D014805:Vitamin B 12