Hypophosphatasia

Hypophosphatasia is a disease that affects the development of bones and teeth. It is caused by the presence of pathogenic variants in the ALPL gene that produces an enzyme involved in the mineralization process.

Hypophosphatasia is a rare metabolic disease caused by a deficiency in the alkaline phosphatase activity of the liver, bone or kidney due to mutations in the non-tissue-specific alkaline phosphatase gene or ALPL. Exact data on its prevalence are not available, although in Europe it is estimated that there is one severe case per 300,000 births.

Symptoms

Symptoms are highly variable, depending on the time of onset and severity up to seven clinical forms are recognized. In the severe perinatal form, patients show markedly impaired bone mineralization and pulmonary insufficiency. The benign perinatal and infantile forms include respiratory complications, generalized demineralization and rachitic changes in the metaphyses. The juvenile form is characterized by low bone mineral density, seizures and rickets while the adult form by an increased risk of stress fractures and early loss of the adult dentition. Finally, in odontohypophosphatasia there is premature loss of fully erupted primary teeth and severe dental caries, and generally no abnormalities in the skeletal system.

Disease management

Treatment of symptoms includes the use of enzyme replacement therapy, in order to restore alkaline phosphatase enzyme activity; respiratory support; maintenance of calcium homeostasis and proper oendocrinologists and orthopedists; pain management; vitamin B6 supplementation; follow-up of renal complications by nephrologists; specific dental care.

Genes analyzed

ALPL

Bibliography

Kishnani PS, Del Angel G, Zhou S, Rush ET. Investigation of ALPL variant states and clinical outcomes: An analysis of adults and adolescents with hypophosphatasia treated with asfotase alfa. Mol Genet Metab. 2021 May;133(1):113-121.

Nunes ME. Hypophosphatasia. 2007 Nov 20 [updated 2022 Apr 7]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

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