WORLD JOURNAL OF ADVANCE
HEALTHCARE RESEARCH

( An ISO 9001:2015 Certified International Journal )

An International Peer Review Journal for Medical Science and Pharma Professionals

An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)

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Indexing

Abstract

HYPOPHOSPHATASIA AND X-LINKED HYPOPHOSPHATEMIA

Dr. Chintan Himmatbhai Desai*

ABSTRACT

Hypophosphatasia is a rare, inherited metabolic disorder in which patients have deficient tissue nonspecific alkaline phosphatase (TNAP) enzymatic activity. Oral manifestations characteristic of various forms of hypophosphatasia can include early loss of deciduous teeth, severe dental caries, and alveolar bone loss. ? In its severest forms (occurring in 1 in 100,000 live births), hypophosphatasia is associated with impaired bone/tooth mineralization and rickets-like symptoms, seizures, and failure to thrive; based on historical data, patients with severe, early onset (i.e., younger than 6 months) forms of the disorder have a high 5-year mortality rate (73%), generally from respiratory failure. ? In 2015, the U.S. Food and Drug Administration (FDA) approved a recombinant form of TNAP enzyme replacement therapy called asfotase alfa (Strensiq®, Alexion Pharmaceuticals, Inc.) for subcutaneous administration in patients with perinatal, infantile, and juvenile-onset forms of hypophosphatasia. ? Treated patients show improvements in overall survival and survival free from invasive mechanical ventilation compared with historical controls. ? Adverse events include injection-site and hypersensitivity reactions and ectopic calcifications in the eye and kidneys. ? X-linked hypophosphatemia, also known as vitamin D-resistant rickets, is an inherited disorder characterized by low levels of phosphate in the blood due to abnormal processing in the kidney, leading to phosphate wasting and resulting in soft, weak bones (rickets). ? X-linked hypophosphatemia is usually diagnosed in childhood and its features can include bowed or bent legs, short stature, bone pain, and severe dental pain, as well as other oral manifestations that include spontaneous dental abscesses. ? In 2018, the FDA approved burosumab-twza (Crysvita™, Ultragenyx Pharmaceuticals, Inc.), a monoclonal antibody that inhibits activity of excess fibroblast growth factor 23, thereby restoring normal renal phosphate processing for adult and pediatric individuals with X-linked hypophosphatemia. ? Treated patients show improvements in serum phosphate levels and radiologic findings, compared to placebo treatment or to historical controls. ? Adverse events include injection-site reaction, headache, and decreased circulating levels of vitamin D.

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