Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy

The Clinical Biochemist. Reviews
Jean Pierre Salles

Abstract

Hypophosphatasia (HPP) is a rare inherited systemic metabolic disease caused by mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. TNSALP is expressed in the liver, kidney and bone, and its substrates include TNSALP inorganic pyrophosphate, pyridoxal-5'-phosphate (PLP)/vitamin B6 and phosphoethanolamine (PEA). Autosomal recessive and dominant forms of the disease result in a range of clinical entities. Major hallmarks are low alkaline phosphatase (ALP) and elevated PLP and PEA levels. Very severe infantile forms of HPP cause premature death as a result of respiratory insufficiency and also present with hypo-mineralisation leading to deformed limbs with, in some cases, the near-absence of bones and skull altogether. Respiratory failure, rib fractures and seizures due to vitamin B6 deficiency are indicative of a poor prognosis. Craniosynostosis is frequent. HPP leads to an unusual presentation of rickets with high levels of calcium and phosphorus, resulting in hypercalciuria, nephrocalcinosis and low ALP levels. Hypercalcaemic crisis, failure to thrive and growth retardation are concerns in infants. Fractures are common in both infantile and adult forms of the disease, concomitantly occurring with unexplained...Continue Reading

Citations

Jan 30, 2021·Wiener medizinische Wochenschrift·Roland KocijanJochen Zwerina
Feb 14, 2021·Orphanet Journal of Rare Diseases·Elizabeth I PierpontKyriakie M Sarafoglou
Apr 9, 2021·Orphanet Journal of Rare Diseases·Meijuan LiuChunxiu Gong
May 2, 2021·Journal of Clinical Pathology·Jonathan Samuel FennIngrid Borovickova
Jul 16, 2021·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Hugh B QuinnMichael P Kane

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