Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Age of Onset
Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease
Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype
X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder
Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Other Names (AKA)
Phosphoethanol-aminuria; Hypophosphatasia mild; Phosphoethanolaminuria;
Congenital and Genetic Diseases; Metabolic disorders; Mouth Diseases;
Hypophosphatasia (HPP) is a genetic condition that causes abnormal development of the bones and teeth. The severity of HPP can vary widely, from fetal death to fractures that don't begin until adulthood. Signs and symptoms may include poor feeding and respiratory problems in infancy;
The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. Hypophosphatasia weakens and softens the bones, causing skeletal abnormalities similar to another childhood bone disorder called rickets. Affected infants are born with short limbs, an abnormally shaped chest, and soft skull bones. Additional complications in infancy include poor feeding and a 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.
The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have
The mildest form of this condition, called odontohypophosphatasia, only affects the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss, but do not have the skeletal abnormalities seen in other forms of hypophosphatasia.
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
|Medical Terms||Other Names||
|80%-99% of people have these symptoms|
|Abnormality of the dentition||
[ more ]
|Abnormality of the metaphysis||
Abnormality of the wide portion of a long bone
|Abnormality of the ribs||
|Bowing of the long bones||
Bowed long bones
Bowing of long bones
[ more ]
|Failure to thrive in infancy||
Faltering weight in infancy
Weight faltering in infancy
[ more ]
|Feeding difficulties in infancy||0008872|
Low chest circumference
[ more ]
Decreased body height
[ more ]
|Skin dimple over apex of long bone angulation||0001024|
|30%-79% of people have these symptoms|
Low number of red blood cells or hemoglobin
High blood calcium levels
Increased calcium in blood
[ more ]
Low or weak muscle tone
Increased fracture rate
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ]
ALPL mutations that almost completely eliminate alkaline phosphatase activity generally cause the more severe forms of HPP, while mutations that reduce activity to a lesser extent often cause the milder forms of HPP.
- Hydration, restriction of dietary calcium, vitamin D, and sometimes thiazide diuretics for hypercalcemia
- Ventilatory support for severely affected infants, some of which need a tracheostomy, which can lead to problems with speech and language development and tolerance of oral feeds
Physiotherapy, occupational therapy and chronic pain management for pain and motor difficulty
- Surgery for fractures that fail to heal
More recently, research has shown positive effects of human recombinant
Bone marrow and
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.
- Asfotase alfa(Brand name: Strensiq) Manufactured by Alexion Pharmaceuticals, Inc.
FDA-approved indication: For the treatment of patients with perinatal/infantile-and juvenile-onset hypophosphatasia (HPP).
National Library of Medicine Drug Information Portal
Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.
Conditions with similar signs and symptoms from Orphanet
In the prenatal context, the differential diagnosis includes osteogenesis imperfecta, campomelic dysplasia, hypophosphatemic rickets and achondrogenesis. The main differential diagnosis in other forms is osteogenesis imperfecta.
Visit the Orphanet disease page for more information.
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
- Visit the following Facebook groups related to Hypophosphatasia:
The Avalon Foundation
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
- Genetics Home Reference (GHR) contains information on Hypophosphatasia. This website is maintained by the National Library of Medicine.
- The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
- The MAGIC Foundation has an information page about hypophosphatasia.
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Hypophosphatasia. Click on the link to view a sample search on this topic.
- Hypophosphatasia. Genetics Home Reference (GHR). September 2007; https://ghr.nlm.nih.gov/condition=hypophosphatasia.
- Etienne Mornet and Mark E Nunes. Hypophosphatasia. GeneReviews. November, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1150/.
- Morrow T. Expensive New Biologic Helps Children Fight Hypophosphatasia. Manag Care. December, 2015; 24(12):25-26. https://www.managedcaremag.com/linkout/2015/12/25.
- Scott LJ. Asfotase Alfa: A Review in Paediatric-Onset Hypophosphatasia. Drugs. February, 2016; 76(2):255-262.
- Bishop N. Clinical management of hypophosphatasia. Clin Cases Miner Bone Metab. May-August 2015; 12(2):170-173.