Fanconi Renotubular Syndrome 2

A number sign (#) is used with this entry because Fanconi renotubular syndrome-2 (FRTS2) is caused by homozygous mutation in the SLC34A1 gene (182309) on chromosome 5q35. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of Fanconi renotubular syndrome, see FRTS1 (134600).

Clinical Features

Tieder et al. (1988) reported a 14-year-old boy and his 18-year-old sister from a consanguineous Arab family with renal Fanconi syndrome who had severe rickets and osteopenia, marked hypercalciuria without renal tubular acidosis, and, in contrast to previously reported patients with Fanconi renotubular syndrome (see FRTS1, 134600), significantly elevated serum levels of 1,25 dihydroxyvitamin D. Physical examination of the parents and 5 sibs revealed no pathologic findings. Treatment with neutral phosphate resulted in improvement in bone pain, muscle strength, and radiologic signs of rickets, with normalization of urinary calcium excretion and a significant decrease in 1,25(OH)2D. However, the glomerular filtration rate, serum uric acid levels, and rate of urinary excretion of glucose, protein, and amino acids remained unchanged.

Magen et al. (2010) restudied the consanguineous Arab family with renal Fanconi syndrome reported by Tieder et al. (1988) and found that both patients had a generalized proximal tubulopathy, renal phosphate wasting, bone mineral deficiency, and decreased glomerular filtration rates. However, in contrast to the findings 20 years earlier, the patients had normocalciuria and vitamin D deficiency.

Mapping

Magen et al. (2010) performed a genomewide scan in a consanguineous Arab family with renal Fanconi syndrome originally reported by Tieder et al. (1988) and identified a 9.2-Mb segment of shared homozygosity between the affected individuals, flanked by markers rs9313575 and rs6894609 on chromosome 5q35.1-q35.3. A maximum multipoint lod score of 2.4 was obtained, which the authors stated was relatively low due to the low number of affected individuals in the studied pedigree.

Molecular Genetics

In an affected brother and sister from a consanguineous Arab family with renal Fanconi syndrome mapping to chromosome 5q35.1-q35.3, originally reported by Tieder et al. (1988), Magen et al. (2010) analyzed the candidate gene SLC34A1 (182309) and identified homozygosity for an in-frame 21-bp duplication (182309.0003). The unaffected mother and an unaffected brother were heterozygous for the duplication, which was not found in 100 ethnically matched controls.