A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.

We describe two siblings from a consanguineous family with autosomal recessive Fanconi's syndrome and hypophosphatemic rickets. Genetic analysis revealed a homozygous in-frame duplication of 21 bp in SLC34A1, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, as the causative mutation. Functional studies in Xenopus laevis oocytes and in opossum kidney cells indicated complete loss of function of the mutant NaPi-IIa, resulting from failure of the transporter to reach the plasma membrane.

Detection and incidence of anomalies associated with hypospadias.

Hypospadias has been associated with synchronous congenital anomalies, especially in the urogenital system, and routine screening of patients with hypospadias has been advocated. In recent years, ultrasound (US) has replaced intravenous pyelography (IVP) as the primary screening test for urological deformities, yet there has never been a study of the relative diagnostic efficacy of the two tests in these patients. In this study, we assessed the incidence of urogenital and extraurogenital congenital anomalies in our hypospadias patients that were noted during physical examination and/or laboratory and imaging screening, and evaluated the efficacy of our changing routine screening protocols.

SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of autosomal recessive inheritance that was first described in a large consanguineous Bedouin kindred. HHRH is characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histological evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption.

Hereditary hypophosphatemic rickets with hypercalciuria: report of a new kindred.

We report a new kindred of hereditary hypophosphatemic rickets with hypercalciuria. The symptomatic child and several relatives had increased renal phosphate clearance leading to hypophosphatemia, hyperabsorptive hypercalciuria, low PTH and increased 1,25-(OH)2D serum level. However, association with vitamin D deficiency and normal urinary excretion of cyclic AMP might suggest another tubular defect in phosphate transport.

Hereditary hypophosphatemic rickets with hypercalciuria is not caused by mutations in the Na/Pi cotransporter NPT2 gene.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a renal phosphate (Pi) wasting disease first described in an extended Bedouin kindred, is characterized by hypophosphatemia, elevated serum 1,25-dihydroxyvitamin D levels, hypercalciuria, rickets, and osteomalacia. Correction of all abnormalities, except for renal Pi wasting, can be achieved by oral Pi supplementation. These findings and the demonstration that mice that are homozygous for the disrupted Na/Pi cotransporter gene Npt2 exhibit many of the biochemical features of HHRH suggested that mutations in the human orthologue NPT2 might be responsible for HHRH.

Therapy-resistant seizures in pseudohypoparathyroidism. A case report.

A 30 year-old, mentally retarded female presented with uncontrolled seizures. The diagnosis of pseudohypoparathyroidism was established on grounds of clinical, laboratory and radiological evaluation. Despite normalization of serum calcium levels with vitamin D treatment, the patient continued to suffer from frequent convulsions.

The Weismann-Netter, Stuhl syndrome: a rare pediatric skeletal dysplasia.

A 5-year-old girl presented with lower limb deformities, delayed ambulation, short stature, facial dysmorphism and scoliosis. Radiologic examination showed severe anterior and external bowing of the femurs and anterior and internal bowing of the tibia and fibula, with posterior and medial cortical thickening. Square iliac wings, horizontal sacrum and low-set L5 were also seen.

Maffucci's syndrome--the result of neural abnormalities? Evidence of mitogenic neurotransmitters present in enchondromas and soft tissue hemangiomas.

Background: Maffucci's syndrome (MS) is distinguished by the enigmatic association of benign cartilaginous bone tumors and soft tissue hemangiomas.

Methods: This study was conducted to define the distribution of nerves and neuropeptides around these tumors. Results were measured by quantitative image analysis of immunohistochemical staining.

Benign fibroepithelial polyps of the ureter and renal pelvis in childhood. Two case reports.

Benign fibroepithelial polyps of the ureter and renal pelvis are extremely rare in children. Two cases are presented and the clinical and surgical aspects of diagnosis and treatment are discussed.

Hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets.

The treatment of X-linked hypophosphatemia (XLH) consists of phosphate and vitamin D3 derivatives. Transient hypercalciuria and hypercalcemia are well-known signs of vitamin D intoxication. Despite urinary calcium excretion control, the danger of nephrocalcinosis in treated patients has been emphasized.

A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature.

Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a correlative clinical-histomorphometric study.

We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia.

Linear growth in patients with hypophosphatemic vitamin D-resistant rickets: influence of treatment regimen and parental height.

The effects of different treatment regimens and the influence of parental height on the statural growth of 40 patients with hereditary vitamin D-resistant hypophosphatemic rickets were investigated. Three treatment regimens, each with oral phosphate, were used: vitamin D (0.5 to 2 mg/day), calcidiol (50 to 200 micrograms/day), and 1 alpha-hydroxyvitamin D3 (1 to 3 micrograms/day).

Spondyloepiphyseal dysplasia associated with progressive arthropathy. An unusual disorder mimicking juvenile rheumatoid arthritis.

A family is presented with three affected siblings suffering from a rare form of spondyloepiphyseal dysplasia with progressive arthropathy affecting most joints of the body except for the craniofacial skeleton. This syndrome, probably of autosomal recessive inheritance, clinically presents diffuse and chronic joint involvement and should be differentiated from juvenile rheumatoid arthritis and other rheumatic disorders.

Hypercalciuria as a cause of persistent or recurrent haematuria.

Of 91 children with idiopathic persistent or recurrent haematuria, eight also had hypercalciuria. This was transient in three and persistent in five. Persistent hypercalciuria was a rare cause of microscopic haematuria (two of 80), but common in association with gross haematuria (three of 11).

Effect of levamisole on chemotaxis of granulocytes from uremic patients.

Uremic granulocyte chemotaxis was assessed in the presence of four different concentrations of levamisole. Chemotactic responsiveness of uremic granulocytes was significantly decreased compared to normal, both in the absence of levamisole and with all levamisole concentrations tested. However, with 10(-3) and 10(-4) M levamisole concentrations, uremic granulocyte chemotaxis was similar to that of normal granulocytes without levamisole.

1,25-Dihydroxyvitamin D-induced suppressor cells in uremic versus normal lymphocytes.

1,25-Dihydroxyvitamin D3 (DHD) has been shown to suppress mitogen-induced blast transformation. This inhibition is abolished by prior elimination of adherent cells. Chronic renal failure is an immunodeficiency state on the one hand and is associated with abnormalities in vitamin D metabolism on the other.

"Idiopathic" hypercalciuria and hereditary hypophosphatemic rickets. Two phenotypical expressions of a common genetic defect.

Among 59 closely related members of one Bedouin tribe, we identified 9 who had the characteristic features of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We found "idiopathic" hypercalciuria in 21 of the 50 asymptomatic members. The biochemical abnormalities observed in these 21 subjects were qualitatively similar to those in the 9 with HHRH, but were quantitatively milder.

Pneumaturia: need for diagnostic alertness.

Pneumaturia, an air-filled urinary bladder with or without passage of gas in the urine, is a rare phenomenon in the general population, but is more frequent in defined high-risk subgroups. Relevant symptomatology may be hardly noticeable for a relatively long period; however, the outcome may be serious and sometimes fatal. We present three such cases and discuss diagnostic and therapeutic aspects.

Direct measurement of TP/GFR: a simple and reliable parameter of renal phosphate handling.

As the Walton-Bijvoet nomogram for estimating renal phosphate (P) threshold (TmP/GFR) is not applicable to children of all ages, we sought an alternative method for measuring renal handling of P. Recognizing that the nomogram represents an indirect correlation between TmP/GFR and TP/GFR under fasting conditions, we examined this directly in 26 children. An excellent correlation was found, expressed as TmP/GFR = (fasting TP/GFR X 1.

The effects of uremic serum and 3'-5' cyclic AMP on blastogenesis of normal lymphocytes.

Phytohemagglutinin (PHA) induced lymphocyte blast transformation is impaired both in uremic lymphocytes and in normal lymphocytes exposed to uremic serum. Cyclic AMP is known to inhibit blast transformation in normal and uremic lymphocytes. This investigation was undertaken to assess quantitatively the effects of uremic serum and cyclic AMP on blastogenesis of normal lymphocytes.