In this case series study, we describe and discuss the clinical examination, biochemical profile and gene analysis results of the family members (affected and unaffected) of an HHRH patient.
Hypophosphatemia in HHRH leading to elevation in the serum level of 1.25[(OH).sub.2]D which results in hypercalciuria.
It has been demonstrated that mice homozygous for the disrupted NPT2 gene show many of the features of HHRH and that the SLC34A1/NaPi7 gene plays a key role in phosphate homeostasis and in normal skeletal development (12).
Since HHRH is an autosomal recessive disease, biallelic mutations are required for full-scale disease manifestations; loss of one SLC34A3 allele does not always lead to laboratory abnormalities.
Moreover, the concentration of 1.25[(OH).sub.2][D.sub.3] which is very important in differentiating HHRH patients, was not measured in this study.
In conclusion, as the clinical phenotype of HHRH can be quite variable with different penetrance even in the same family with identical mutations, it is not possible to be certain about a genotype-phenotype effect, and a proper diagnosis requires molecular genetic analysis.
Novel NaPi-IIc mutations causing HHRH and idiopathic hypercalciuria in several unrelated families: long-term follow-up in one kindred.
Similar to HHRH, NPHLOP1 is characterized by hypophosphatemia and decreased renal phosphate absorption with an appropriate elevation in serum 1,25(OH)2D.
Treatment is the same as in HHRH. Oral phosphate replacement will result in improvement in bone pain, muscle strength and radiologic signs of rickets, with normalization of urinary calcium excretion and significant decrease in 1,25(OH)2D.
Characteristic clinical features include hypophosphatemia, hypercalcemia, elevated serum levels of 1,25(OH)2D, hypercalciuria, decreased TRP or low TmP/GFR value and nephrolithiasis, which cannot be distinguished from HHRH or NPHLOP1 without molecular testing.