Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Disorders of the renal phosphate transporters

Renal phosphate transporters are sodium-coupled transporters located in the apical membrane of proximal tubular cells. They play an important role in phosphate regulation.

Pathogenesis

Under physiological conditions phosphate is filtered in excess, so the body needs to reclaim large amounts of phosphate to keep the body content stable (60-80%). This resorption is accomplished by renal phosphate transporters. Inactivation of those transporters may result in excessive urinary phosphate loss and bone destruction ensue.

Renal phosphate transporters are located in the proximal tubule. The figure below shows its distribution along the segments. While the transporter SLC34A1 can be found in all three segments the other two are localized in the first two segments only.

[Error: Macro 'dot' error: dot() got an unexpected keyword argument 'title']

Under physiological conditions theTrasnporter SLC20A2 has no effect on phosphate handling as dysfunction can be easily compensated by the other two transporters. Therefore no mutation with bone or kidney phenotype is known so far. However, it seems plausible that variation in this gene too may contribute to a phenotype caused by mutations in other genes.

Systematic

Hypophosphatemic bone and kindney disease
Disorders of the renal phosphate transporters
Hypophosphatemic rickets with hypercalciuria
SLC34A3
Idiopathic basal ganglia calcification 1
SLC20A2
Nephrolithiasis/osteoporosis, hypophosphatemic, 1
SLC34A1
Nephrolithiasis/osteoporosis, hypophosphatemic, 2
SLC9A3R1
FGF23-induced hypophosphatemic rickets
Fanconi-type hypophosphatemic rickets
Hypophosphatemic rickets with hyperparathyroidism
Osteoglophonic dysplasia
Raine syndrome
X-linked dominant hypophosphatemic rickets

References:

1.

Geschwind DH et. al. (1999) Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease).

[^]
2.

Brodaty H et. al. (2002) Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q.

[^]
3.

Oliveira JR et. al. (2004) Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease).

[^]
4.

Dai X et. al. (2010) Identification of a novel genetic locus on chromosome 8p21.1-q11.23 for idiopathic basal ganglia calcification.

[^]
5.

Wang C et. al. (2012) Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis.

[^]
6.

Hsu SC et. al. (2013) Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.

[^]
7.

Karim Z et al. (2008) NHERF1 mutations and responsiveness of renal parathyroid hormone.

[^]
8.

None (1979) Familial basal ganglia calcification and schizophreniform psychosis.

[^]
9.

Koller WC et. al. (1979) Calcification of the basal ganglia: computerized tomography and clinical correlation.

[^]
10.

Boller F et. al. (1977) Familial idiopathic cerebral calcifications.

[^]
11.

Flint J et. al. (1992) Familial calcification of the basal ganglia: a case report and review of the literature.

[^]
12.

Förstl H et. al. (1992) Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation.

[^]
13.

Manyam BV et. al. (1992) Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies.

[^]
14.

Ellie E et. al. (1989) Familial idiopathic striopallidodentate calcifications.

[^]
15.

Babbitt DP et. al. (1969) Idiopathic familial cerebrovascular ferrocalcinosis (Fahr's disease) and review of differential diagnosis of intracranial calcification in children.

[^]
16.

Moskowitz MA et. al. (1971) Familial calcification of the basal ganglions: a metabolic and genetic study.

[^]
17.

Harati Y et. al. (1984) Adult onset idiopathic familial brain calcifications.

[^]
18.

Smits MG et. al. (1983) Progressive idiopathic strio-pallido-dentate calcinosis (Fahr's disease) with autosomal recessive inheritance. Report of three siblings.

[^]
19.

Harrington MG et. al. (1981) The significance of the incidental finding of basal ganglia calcification on computed tomography.

[^]
20.

Puvanendran K et. al. (1980) Idiopathic familial basal ganglia calcification associated with juvenile hypertension.

[^]
21.

None (1995) Non-progressive familial idiopathic intracranial calcification: a family report.

[^]
22.

Martinelli P et. al. (1993) Familial idiopathic strio-pallido-dentate calcifications with late onset extrapyramidal syndrome.

[^]
23.

Kobari M et. al. (1997) Familial idiopathic brain calcification with autosomal dominant inheritance.

[^]
24.

Manyam BV et. al. (2001) Bilateral striopallidodentate calcinosis: clinical characteristics of patients seen in a registry.

[^]
25.

Manyam BV et. al. (2001) Parkinsonism associated with autosomal dominant bilateral striopallidodentate calcinosis.

[^]
26.

None (1957) Familial calcification of the basal ganglia with response to parathormone.

[^]
27.

None (1958) [Familial symmetrical brain calcification].

[^]
28.

NICHOLS FL et. al. (1961) Familial hypocalcemia, latent tetany and calcification of the basal ganglia. Report of a kindred.

[^]
29.

BRUYN GW et. al. () FAMILIAL BILATERAL VASCULAR CALCIFICATION IN THE CENTRAL NERVOUS SYSTEM.

[^]
30.

None (1959) Familial calcification of the cerebral basal ganglia and its relation to hypoparathyroidism.

[^]
31.

None (1951) Calcification of the corpus stiatum and dentate nuclei occurring in a family.

[^]
32.

None (2005) What is and what is not 'Fahr's disease'.

[^]
33.

Lester J et. al. (2006) Diffuse intracranial calcinosis: Fahr disease.

[^]
34.

Weisman DC et. al. (2007) Density of the brain, decline of the mind: an atypical case of Fahr disease.

[^]
35.

Yamada M et. al. (2014) Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan.

[^]
Update: Sept. 26, 2018