Homepage > Rare diseases > Search

Search for a rare disease

*
(*) mandatory field

Adult hypophosphatasia

Suggest an update
Your message has been sent Your message has not been sent. Please contact an administrator.
Disease definition

A moderate form of hypophosphatasia (HPP) characterized by adult onset osteomalacia, chondrocalcinosis, osteoarthropathy, stress fractures and dental anomalies.

ORPHA:247676

Classification level: Subtype of disorder

Synonym(s):
  • Adult Rathbun disease
  • Adult phosphoethanolaminuria

Prevalence: Unknown

Inheritance: Autosomal dominant, Autosomal recessive

Age of onset: Adult

ICD-10: E83.3

ICD-11: 5C64.3

OMIM: 146300

UMLS: C0268413

MeSH: C562647

Summary
Epidemiology

The prevalence of adult hypophosphatasia is not known. However the prevalence of moderate HPP (childhood, adult and odontoHPP) cases taken together has been estimated at 1/6300.

Clinical description

Adult HPP is clinically very heterogeneous. In its mildest form it is the least severe form of hypophosphatasia (HPP), characterized by non-specific symptoms in later age, such as osteoporosis, musculoskeletal pain, chondrocalcinosis. Most patients present features during middle age but some may have had a history of mild rickets or other musculoskeletal manifestations in childhood. Cardinal features include stress fractures and pseudo-fractures of the lower limbs, along with foot, thigh, and hip pain. The most common fracture types are metatarsal and tibial and femoral pseudofractures. Osteomalacia, chondrocalcinosis, and osteoarthropathy may develop with age. Some patients report history of early loss of primary dentition. Loss of permanent dentition is also common and some cases of enamel hypoplasia and tooth mobility are described. Patients with the adult form of HPP may have had some manifestations in early life between the prenatal period and childhood (prenatal benign HPP or childhood HPP). The presence of bone symptoms (osteomalacia, fractures) distinguish adult HPP from odontohypophosphatasia.

Etiology

Mutations in the ALPL gene (1p36.12) are known to cause hypophosphatasia.

Diagnostic methods

Diagnosis is based on clinical presentation, alkaline phosphatase assay and confirmed by genetic testing.

Differential diagnosis

The main differential diagnosis is osteogenesis imperfecta.

Genetic counseling

Inheritance may be autosomal recessive (rare) or autosomal dominant (the vast majority of cases).

Management and treatment

Management is typically supportive.

Prognosis

Overall prognosis is typically good, although affected individuals may experience some physical limitations depending on the extent and progression of the disease.

Last update: February 2020 - Expert reviewer(s): Dr Severine BACROT - Dr Etienne MORNET
A summary on this disease is available in Français, Español, Deutsch, Italiano, Português, Nederlands Polski
Detailed information

Logo ERN: produced/endorsed by ERN(s) Logo FSMR: produced/endorsed by FSMR(s)

General public
Article for general public
Svenska (2016) - Socialstyrelsen
Guidelines
Emergency guidelines
Français (2021.pdf) - Orphanet Urgences
Clinical practice guidelines
English (2020) - Osteoporos Int Logo ERN
Disease review articles
Review article
English (2007) - Orphanet J Rare Dis
Clinical genetics review
English (2025) - GeneReviews
Genetic testing
Guidance for genetic testing
English (2010) - Eur J Hum Genet
Diagnostic Keys
Français (2024) - Les clés du diagnostic Logo FSMR
Français (2024) - Les clés du diagnostic Logo FSMR
Français (2024) - Les clés du diagnostic Logo FSMR
Français (2024) - Les clés du diagnostic Logo FSMR
Français (2024) - Les clés du diagnostic Logo FSMR
The documents contained in this website are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.