Hypophosphatasia: an overview of the disease and its treatment

Area of Science:

• Genetics and rare diseases
• Biochemistry
• Medical genetics

Background:

• Hypophosphatasia (HPP) is a rare inherited metabolic disorder.
• It results from deficient activity of tissue-non-specific alkaline phosphatase (TNSALP).
• HPP exhibits wide clinical variability, ranging from lethal to mild forms.

Purpose of the Study:

• To review current knowledge on hypophosphatasia.
• To detail the genetics, epidemiology, and clinical spectrum of HPP.
• To survey current and emerging therapeutic strategies.

Main Methods:

• Literature review of hypophosphatasia.
• Analysis of TNSALP genetics and mutations.
• Compilation of epidemiological data and clinical classifications.
• Survey of treatment approaches, including enzyme replacement therapy.

Main Results:

• HPP is caused by mutations in the TNSALP gene.
• Six distinct clinical forms of HPP are identified: perinatal lethal, prenatal benign, infantile, childhood, adult, and odontohypophosphatasia.
• Diagnostic clues and therapeutic options are presented.

Conclusions:

• Hypophosphatasia is a serious genetic disorder with diverse manifestations.
• Accurate diagnosis relies on understanding TNSALP genetics and clinical presentation.
• Enzyme replacement therapy shows promise for treating HPP.