Meyahealth
HomeGeneticsConditionHypophosphatasia
Back to Condition
Hypophosphatasia
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Hypophosphatasia

Hypophosphatasia is an inherited disorder that disrupts the mineralization of bones and teeth, leading to skeletal abnormalities and dental complications.

Overview

Hypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.

Symptoms

The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood.

  • Infancy: The most severe forms occur before birth or in early infancy. Infants may be born with short limbs, an abnormally shaped chest, and soft skull bones. Complications include poor feeding, failure to gain weight, respiratory problems, and high levels of calcium in the blood (hypercalcemia), which can lead to recurrent vomiting and kidney problems. These complications are life-threatening in some cases.
  • Childhood: Early loss of primary (baby) teeth is often one of the first signs. Children may have short stature with bowed legs, enlarged wrist and ankle joints, and an abnormal skull shape.
  • Adulthood: Characterized by a softening of the bones known as osteomalacia. Recurrent fractures in the foot and thigh bones can lead to chronic pain. Adults may lose their secondary (adult) teeth prematurely and are at increased risk for joint pain and inflammation.
  • Odontohypophosphatasia: The mildest form, which only affects the teeth, causing abnormal tooth development and premature tooth loss without skeletal abnormalities.

Frequency

Severe forms of hypophosphatasia affect an estimated 1 in 100,000 newborns. Milder cases, such as those that appear in childhood or adulthood, probably occur more frequently. The condition is most common in white populations and is particularly frequent in a Mennonite population in Manitoba, Canada, where about 1 in 2,500 infants is born with severe features.

Causes

Mutations in the ALPL gene cause hypophosphatasia. This gene provides instructions for making an enzyme called tissue-nonspecific alkaline phosphatase (TNSALP), which plays an essential role in the mineralization of the skeleton and teeth. Mutations lead to an abnormal version of TNSALP that cannot participate effectively in mineralization. This allows substances like inorganic pyrophosphate (PPi) to build up, which interferes with the hardening of bones and teeth.

Gene Associated with Hypophosphatasia

  • ALPL

Inheritance

Severe forms of hypophosphatasia that appear early in life are inherited in an autosomal recessive pattern, meaning two copies of the gene in each cell are altered. Milder forms can be inherited in an autosomal recessive or autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder.

Other Names for This Condition

  • Deficiency of alkaline phosphatase
  • Phosphoethanolaminuria

Frequently Asked Questions

The only disease‑specific therapy approved in many countries is asfotase alfa, a recombinant alkaline phosphatase enzyme replacement given by subcutaneous injection. It helps restore bone mineralization and can lower serum calcium. Supportive care includes careful hydration, monitoring kidney function, and, if needed, temporary use of bisphosphonates or diuretics to control calcium levels under specialist supervision.
While enzyme replacement is generally reserved for more severe disease, adults can benefit from weight‑bearing exercise (e.g., walking, resistance training), adequate vitamin D and calcium intake (but not excessive calcium, which can worsen hypercalcemia), and avoidance of smoking and excessive alcohol. Periodic bone density scans guide the need for additional therapies such as teriparatide, which some clinicians use off‑label after careful risk assessment.
Premature loss of primary teeth—especially without obvious decay or trauma—is a classic early clue for hypophosphatasia. The teeth often fall out with little or no root resorption, and the crowns may appear unusually small or malformed. If you notice this pattern, especially together with bowed legs, short stature, or a family history of bone problems, ask your pediatrician for serum alkaline phosphatase testing and genetic evaluation.
Testing usually starts with a blood sample for DNA sequencing of the ALPL gene, which encodes tissue‑non‑specific alkaline phosphatase. If a pathogenic variant is identified, targeted testing can be offered to at‑risk relatives. Because the disorder can be inherited in an autosomal recessive or, less commonly, autosomal dominant pattern, carrier testing for siblings and prenatal or pre‑implantation genetic diagnosis for future pregnancies are options to discuss with a genetic counselor.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ