Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Disturbances in phosphate metabolism

Disturbances in phosphate handling include diseases with hypophosphatemia and hyperphosphatemia. The former is caused by excessive renal phosphate wastage and results in bone disorders, such as rickets, osteomalacia, osteoporosis, and osteoglophonia. Hyperphosphatemia on the other hand is caused by renal phosphate Retention and results in excessive bone ossification (osteopetrosis, subperiostal bone formation and calcinosis.

Pathogenesis

The flowchart below shows normal phosphate metabolism as it is designed to stabilize body phosphate content (homeostasis). With our normal diet, we consume phosphate in excess. Excess phosphate is excreted renally. By the amount of reabsorbed phosphate homeostasis is controlled. As with a normal diet 80% of the filtrated phosphate is reabsorbed, this leaves enough room to regulate homeostasis through a wide range of phosphate intake.

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As renal reabsorption is the key player in phosphate homeostasis, it is there where most control is excreted. The control mechanisms that down-regulate reabsorption and by that up-regulate excretion are marked red. Disturbances of these control mechanisms eventually lead to phosphate wastage or phosphate retention, two sides of the same coin, disturbances of phosphate metabolism.

Management

As hyper- and hypophosphatemia are managed differently the specific recommendations can be found there.

Systematic

Hereditary metabolic diseases
Aceruloplasminemia/Hypoceruloplasminemia
Coenzyme Q10 deficiency
Congenital disorder of glycosylation
Disorders of cobalamin metabolism
Disorders of iron metabolism
Disorders of urate metabolism
Disturbances in phosphate metabolism
Hyperphosphatemic familial tumoral calcinosis
FGF23
GALNT3
KL
Hypophosphatasia
Adult hypophosphatasia
ALPL
Childhood hypophosphatasia
ALPL
Infantile hypophosphatasia
ALPL
Odontohypophosphatasia
ALPL
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
Autosomal dominant hypophosphatemic rickets
FGF23
Autosomal recessive hypophosphatemic rickets type 1
DMP1
Autosomal recessive hypophosphatemic rickets type 2
ENPP1
X-linked dominant hypophosphatemic rickets
PHEX
Fanconi-type hypophosphatemic rickets
Nephrolithiasis/osteoporosis, hypophosphatemic, 1
SLC34A1
X-linked recessive hypophosphatemic rickets
CLCN5
OCRL
Hypophosphatemic rickets with hyperparathyroidism
KL
Osteoglophonic dysplasia
FGFR1
Raine syndrome
FAM20C
X-linked dominant hypophosphatemic rickets
PHEX
Disturbances of glucose metabolism
Food intolerance
Genetic hyperbilirubinemia
Glycolipidosis
HADH deficiency
Hereditary lipid disorders
Hypercatabolic hypoproteinemia
Hypomagnesemia
Hypomethylation syndrome
Lysosomal storage disease
MELAS syndrome
Methionine adenosyltransferase deficiency
Methylmalonic aciduria
Urea cycle disorders

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Update: Sept. 26, 2018