Elevated Serum 1,25-Dihydroxyvitamin D Concentrations in Siblings with Primary Fanconi's Syndrome

Tieder, M; Arie, R.; Modai, David; Samuel, R.; Weissgarten, Joshua; Liberman, Uri

doi:10.1056/nejm198809293191307

Cited by 60 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, no correlation was found between growth retardation and hypokalemia, but it is noteworthy that two patients who never required K supplements had the greatest height SDS at the last observation. Severe stunting may occur in the absence of hypokalemia, as demonstrated in patients 7 and 9 and in some FS patients reported in the literature [22,27,36].…”

Section: Discussionmentioning

confidence: 71%

Body growth in primary de Toni-Debré-Fanconi syndrome

Haffner

Weinfurth

Seidel

et al. 1997

Pediatric Nephrology

View full text Add to dashboard Cite

Body growth in nine children with primary de Toni-Debré-Fanconi syndrome was followed from birth to adolescence or adult life. At the time of diagnosis, corresponding to the start of treatment, the median age was 2.3 (range 0.4-13.9) years and height standard deviation score (SDS) was always decreased (median -3.5, range -6.8 to -2.1). Despite continuous electrolyte and bicarbonate supplementation only four patients showed a slight improvement in growth. At the time of the last observation at the age of 17.2 (4.5-20.1) years median height was -4.7 (-5.9 to -1.8) SDS. The median difference between height at last observation and target height was -4.5 SDS. Final height (n = 5) ranged between -1.8 and -5.5 (median -4.3) SDS. The pubertal growth spurt was absent in two children. Metabolic acidosis was identified as a significant growth-retarding factor. Mean serial blood bicarbonate levels and height SDS at the last observation were correlated (r = -0.87, P < 0.01). No correlation was observed between last height SDS and the degree of hypokalemia, hypophosphatemia, or hypercalciuria. In conclusion, patients with primary de Toni-Debré-Fanconi-syndrome present severe growth failure at the time of diagnosis which persists into adult life. Supportive therapy is frequently unable to prevent further loss of relative height.

show abstract

Section: Discussionmentioning

confidence: 71%

Body growth in primary de Toni-Debré-Fanconi syndrome

Haffner

Weinfurth

Seidel

et al. 1997

Pediatric Nephrology

View full text Add to dashboard Cite

show abstract

“…A recessive lossof-function mutation in SLC34A1 was described in two siblings with renal Fanconi's syndrome, hypophosphatemic rickets, hypercalciuria, and elevated 1,25-(OH) 2 D 3 levels. 20,21 Unfortunately, no data regarding the clinical course during infancy were reported. A recent report describes two siblings with a homozygous missense mutation who presented with hypophosphatemia and nephrocalcinosis.…”

Section: Discussionmentioning

confidence: 99%

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

Schlingmann

Ruminska

Kaufmann

et al. 2016

Journal of the American Society of Nephrology

227

192

View full text Add to dashboard Cite

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D 3 -24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH) 2 D 3 . In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH) 2 D 3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH.

show abstract

“…However, the genetic transmission of hypophosphatemic rickets with hypercalciuria is autosomal recessive and not X-linked dominant. Liberman (36) has also reported the existence of a Fanconi syndrome variant in which renal phosphate wasting and hypophosphatemia occur in concert with normally regulated vitamin D metabolism. A similar association has not yet been observed in patients with a rachitic/osteomalacic disease transmitted in an X-linked dominant fashion.…”

Section: Discussionmentioning

confidence: 99%

Normal Regulation of Calcitriol Production in Gy-Mice: Evidence for Biochemical Heterogeneity in the X-Linked Hypophosphatemic Diseases.

DREZNER,

DAVIDAI,

NESBITT

1988

Vitamin D

View full text Add to dashboard Cite

Phenotypic heterogeneity in X-linked hypophosphatemic rickets (XLH) is ascribed to variable penetrance of the genetic abnormality. However (4.7±0.3 mg/dl) and phosphate (P)-depleted mice (4.9±0.4) was significantly less than normal (8.4±0.5). Consistent with P depletion, the Gy mice exhibited enhanced renal 25(OH)Dla-hydroxylase activity (9.3±0.6 fmol/mg kidney per min), similar to that of P-depleted normals (9.1±1.5), but significantly greater than that of controls (3.1±0.3). Such normal enzyme responsiveness was confirmed upon PTH stimulation (1 IU/h s.c.), which revealed that Gy mice increased renal 1-hydroxylase (59±7.7) similarly to normals (65±7.7) and Pdepleted animals (58.4±7.8). Calcitonin administration also enhanced enzyme function comparably in the animal models. Evidence confirming normally responsive calcitriol production in untreated Gy mice included increased serum 1,25-dihydroxyvitamin D levels, gastrointestinal calcium absorption, and urinary calcium. The normally regulated vitamin D metabolism in Gy mice indicates that biochemically diverse disease may result from mutations in the gene family regulating renal P transport and underlying X-linked hypophosphatemia. We suspect such heterogeneity is due to altered P transport at variable segments of the proximal convoluted tubule. (J. Clin. Invest. 1990. 85:334-339.) calcitriol -hypophosphatemia.

show abstract

Elevated Serum 1,25-Dihydroxyvitamin D Concentrations in Siblings with Primary Fanconi's Syndrome

Cited by 60 publications

References 24 publications

Body growth in primary de Toni-Debré-Fanconi syndrome

Body growth in primary de Toni-Debré-Fanconi syndrome

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

Normal Regulation of Calcitriol Production in Gy-Mice: Evidence for Biochemical Heterogeneity in the X-Linked Hypophosphatemic Diseases.

Contact Info

Product

Resources

About