An Expert Perspective on Phosphate Dysregulation With a Focus on Chronic Hypophosphatemia

Abstract

Because of their rarity, diseases characterized by chronic hypophosphatemia can be underrecognized and suboptimally managed, resulting in poor clinical outcomes. Moreover, serum phosphate may not be measured routinely in primary care practice. Authors participated in several working sessions to advance the understanding of phosphate homeostasis and the causes, consequences, and clinical implications of chronic hypophosphatemia. Phosphate levels are regulated from birth to adulthood. Dysregulation of phosphate homeostasis can result in hypophosphatemia, which becomes chronic if phosphate levels cannot be normalized. Chronic hypophosphatemia may be underrecognized as serum phosphate measurement is not always part of routine analysis in the primary care setting and results might be misinterpreted, for instance, due to age-specific differences not being accounted for and circadian variations. Clinical consequences of chronic hypophosphatemia involve disordered endocrine regulation, affect multiple organ systems, and vary depending on patient age and the underlying disorder. Signs and symptoms of chronic hypophosphatemic diseases that manifest during childhood or adolescence persist into adulthood if the disease is inadequately managed, resulting in an accumulation of clinical deficits and a progressive, debilitating impact on quality of life. Early identification and diagnosis of patients with chronic hypophosphatemia is crucial, and clinical management should be started as soon as possible to maximize the likelihood of improving health outcomes. Furthermore, in the absence of a universally accepted description for "chronic hypophosphatemia," a definition is proposed here that aims to raise awareness of these diseases, facilitate diagnosis, and guide optimal phosphate management strategies by improving monitoring and assessment of patient response to treatment.

Establishing the Prevalence of Osteomalacia in Arab Adolescents Using Biochemical Markers of Bone Health

“…For the purpose of this study, biochemical osteomalacia was defined as a combination of any two of the four serum markers of impaired mineralization [8], namely low 25 hydroxyvitamin D (25OHD < 30 nmol/L), high ALP (age-and sex-specific adjusted reference ranges obtained from the CALIPER study [19]), and either low calcium (<2.1 mmol/L) and/or low Pi (age-and sex-adjusted reference ranges) [20], as provided in Table S1.…”

The basics of phosphate metabolism

“…The main symptoms can be explained on a cellular level by energy depletion due to insufficient ATP production. Symptoms include muscle weakness, including respiratory muscles with respiratory failure, bone pain and loss, neuropathies, tremors and seizures, haemolysis and anaemia, metabolic acidosis and insulin resistance [ 103 , 104 ]. In children, rickets and bone deformities are prominent.…”

“…In children, inborn defects of phosphate metabolism are among the most frequent causes and can be caused by gene defects in either renal phosphate transporters or in endocrine regulators [ 26 ]. The most common form of inherited hypophosphataemia is due to mutations in the PHEX gene causing X-linked hypophosphataemia [ 103 ]. In adults, hypophosphataemia can be caused by reduced intestinal absorption, internal shifts or renal losses [ 104 ].…”

The Ip6k1 and Ip6k2 Kinases Are Critical for Normal Renal Tubular Function

“…Hyperphosphatemia associates with cardiovascular disease, whereas hypophosphatemia affects bone and energy metabolism. 1,2 Therefore, circulating phosphate levels must be tightly controlled. In mammals, phosphate homeostasis is ultimately achieved by coordinating intestinal and renal (re)absorption of phosphate.…”