The reference OMIM entry for this protein is 143870

Hypercalciuria, absorptive, 2; hca2
Hypercalciuria, familial idiopathic

A number sign (#) is used with this entry because variation in the soluble adenylyl cyclase gene (SAC; 605205) contributes to susceptibility to the form of absorptive hypercalciuria that has been mapped to 1q23.3-q24 (HCA2). A locus for absorptive hypercalciuria has been mapped to 4q33-qter (HCA1; 607258).

CLINICAL FEATURES

Coe et al. (1979) studied the families of 9 patients with idiopathic hypercalciuria and recurrent calcium oxalate stones. In 26 of 73 relatives, hypercalciuria was found, occurring in 3 consecutive generations of 2 families and in 2 successive generations of 4 other families. Nineteen of 44 first-degree relatives (43%) had idiopathic hypercalciuria. All 19 formed renal stones. Nine of the 19 were women. I have personal experience of idiopathic hypercalciuria with stone formation in monozygotic twin brothers who have several first-degree relatives with hypercalciuric renal stones. Pak et al. (1981) concluded that the disorder is an absorptive hypercalciuria. In the kindred they studied, 12 persons in 3 generations were affected in a pattern consistent with autosomal dominant inheritance. Tieder et al. (1985) suggested that the new entity they described as hereditary hypophosphatemic rickets with hypercalciuria (241530) may be at one end of the spectrum of hereditary absorptive hypercalciurias. This does not necessarily mean that it is a disorder allelic to familial idiopathic hypercalciuria. Tieder et al. (1987) interpreted evidence from studies in 1 Bedouin tribe as indicating that hypercalciuria was the heterozygous manifestation of the disorder which in homozygotes was accompanied by bone disease. Bianchi et al. (1988) found that patients with hypercalciuria had increased erythrocyte-membrane calcium-magnesium-ATPase activity and increased sodium-potassium pump activity. No significant difference from controls was found in erythrocyte sodium-potassium cotransport, sodium-lithium countertransport, or potassium content. In 66 patients with kidney stones, Bianchi et al. (1988) found that 24-hour urinary calcium excretion correlated with erythrocyte-calcium-magnesium ATPase activity. In a study of 30 healthy families, they found a significant correlation between mean values in parents and those in offspring for calcium-magnesium-ATPase and urinary calcium excretion, with no significant correlations between parents with respect to these measures. Bushinsky and Favus (1988) showed that genetic hypercalciuria in rats is due to a primary intestinal overabsorption of dietary calcium and not due to an overproduction of 1,25(OH)(2)D(3) or a defect in the renal tubular reabsorption of calcium. The genetics of hypercalciuria in the rat is not clear from the report by Bushinsky and Favus (1988); they established their colony of genetically hypercalciuric rats by inbreeding which, as they stated, 'results in enrichment of hypercalciuria among offspring.'

MAPPING

Reed et al. (1999) studied 3 kindreds with a severe form of absorptive hypercalciuria by genomewide linkage analysis. They found that the HCA phenotype in these kindreds, characterized by hyperabsorption of calcium and hypercalciuria, was linked to chromosome 1q23.3-q24. A 2-point lod score of 3.3 was obtained with markers D1S318 and D1S196 at a recombination frequency of 0.0. Nonparametric multipoint linkage analysis yielded a peak nonparametric linkage Zall score of 12.7 with p of 6 x 10-6. Analysis of key recombinants within the families studied l ... More on the omim web site

Subscribe to this protein entry history

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 143870 was added.