Review Article
Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders
Figure 11
Schematic diagram of the pathogenesis of CMD. PPi is generated from ATP hydrolysis intracellular by the mitochondria (Mito) or extracellular by the transmembrane enzyme nucleoside triphosphate pyrophosphohydrolase (NTP-PPH). PPi generated intracellular is exported by ANK transporter to the extracellular one and is hydrolysed into two Pi by alkaline phosphatase (ALP) (a). Loss of function mutation in ANK leads to accumulation of PPi intracellular. Absence of extracellular PPi results in excessive bone formation due to increased deposition of bone minerals; hydroxyapatite (HA) crystals made of basic calcium phosphate (BCP), responsible for CMD phenotype in humans (b).
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