Table of ContentsView AllTable of ContentsSelf-ChecksPhysical ExaminationLabs and TestsImagingDifferential DiagnosisNext in Hypophosphatasia GuideWhat Is Hypophosphatasia?
Table of ContentsView All
View All
Table of Contents
Self-Checks
Physical Examination
Labs and Tests
Imaging
Differential Diagnosis
Next in Hypophosphatasia Guide
Hypophosphatasia(HPP) is a rare, inherited skeletal disorder that causes bones and teeth to become soft and weak. With HPP, mineralization—the deposition of calcium and phosphorus into the bones and teeth—becomes impaired.
This leaves the bones vulnerable to fracture, underdevelopment, and deformity. It also causes premature tooth loss.
It is important to diagnose HPP as soon as possible so that treatment can start. But because HPP is so rare, diagnosing it is sometimes hard. This is because it shares signs and symptoms of other more common diseases and affects many different parts of the body.
This article will discuss how HPP is diagnosed using different methods, including self-checks, physical examination, lab work, and more.
Andrew Brookes / Getty Images
There are no home tests or self-exams to diagnose HPP. However, recognizing the signs and symptoms of each type of HPP can help you seek a timely diagnosis.
Childhood HPP symptoms will vary from person to person.Symptoms may include:
Symptoms of adult HPP might include:
It is not usual for adults who receive an HPP diagnosis to report having had symptoms of the condition in childhood.
Skeletal
Skeletal abnormalities of HPP include fractures that don’t heal well and these other bone conditions:
Dental
The earliest dental sign of HPP in children is premature loss of primary teeth.Childhood HPP also causes the decreased height of thealveolar bone(the thick ridge of bone that contains the tooth sockets) and variousmalocclusions, including overbite, underbite, overcrowding, and spacing.
In adults, HPP leaves the gums and teeth vulnerable toperiodontal diseaseand the loss of bony supports that hold the teeth to the jaw.Premature tooth loss is also common with HPP.
Muscular
Childhood HPP affects sitting, crawling, and walking, and might lead to developmental delays.Both adults and children with HPP can experience muscle pain, muscle weakness, and poor muscle tone.
What Are Muscular System Diseases?
Respiratory
Infants with HPP often have chest and rib deformities that make them more vulnerable topneumonia(lung infection).Some infants might develop pulmonary insufficiency and breathing difficulties.
The weakened ribs will produce inflammation over thediaphragm, and thesternumwill be pulled into what is called apigeon breast deformity(pectus carinatum).Additional respiratory signs in infant and childhood HPP include fever and tender rib joints.
Adult HPP is also linked to severe respiratory and pulmonary problems.These are often the result of chest deformities.
Renal
Both children and adults with HPP can suffer from renal (kidney) symptoms, resulting from defective bone mineralization and impaired regulation ofphosphorusandcalcium.In fact, people with HPP are at a greater than the typical risk for kidney damage.
The treating physician will ask about burning, pain, or blood with urination, kidney pain, and frequent urination. They will also check blood pressure levels and ask about signs ofhigh blood pressure, such as frequent headaches, blurred vision, nosebleeds, andfatigue.
Neurologic
Neurologic symptoms of HPP include increasedintracranial pressureand seizures. The treating provider will ask about seizures, headache, blurred vision, confusion, vomiting, behavior changes, and lack of energy or severe fatigue. They will also check blood pressure and for signs ofshallow breathing.
An ALPL mutation results in TNSALP that cannot break down PPi, PLP, and PEA. These substances will accumulate to abnormal levels in the body. The accumulation of PPi is responsible for defective mineralization in HPP.
Different lab tests, including blood and urine, can assist in making an HPP diagnosis.
Genetic Testing
Genetic testingfor the ALPL gene mutation is not always necessary. However, lab testing can be helpful for milder forms of HPP and ruling out other conditions that cause similar symptoms.Genetic testing is also helpful for people who have a family history of HPP and plan future pregnancies.
During pregnancy, chorionic villus sampling (CVS) can test for ALPL gene mutations. With CVS, tissue samples from the placenta are taken for analysis to confirm or rule out an HPP.
Ultrasounds,X-rays,magnetic resonance imaging(MRI), andcomputed tomography(CT) scans are used to aid in making an HPP diagnosis.
X-rays, MRIs, and CT scans can help diagnose HPP at all stages of life—from birth into adulthood. They can also help determine the severity of the condition based on how affected bones are.
Odontohypophosphatasia
Adults and children with odontohypophosphatasia do not have bone disease findings on imaging.A treating physician will rely on analysis of signs, symptoms, and lab work to determine the type of HPP.
If HPP is suspected based on blood and other lab work, doctors rely on cone-beam computed tomography (CBCT) to assess the causes of premature tooth loss.CBCT dental imaging can show short tooth roots, decreases in alveolar bone heights, and various dental malocclusions.
In determining whether a person has HPP, it is important to rule out other conditions whose symptoms might be similar.
Conditions that need to be ruled out or considered (differential diagnosis) include osteomalacia due tohypophosphatemiaand osteomalacia due tovitamin D deficiency, rickets, and other types of other skeletal dysplasias (e.g., osteogenesis imperfecta, campomelic dysplasia, achondrogenesis subtypes, hypochondrogenesis, cleidocranial dysplasia).
What sets HPP aside from similar conditions is the serum concentrations of ALP, PLP, and PEA. Additionally, genetic testing for ALPL mutations can confirm a diagnosis, if uncertain.
Imaging studies are not always reliable, as their findings can overlap with other skeletal dysplasias. Certain features—hypomineralization, bone spurs, and others—might be helpful, but ALPL gene mutation testing is the easiest and most accurate way to confirm a diagnosis when other lab findings are inclusive.
Summary
Hypophosphatasia is a rare inherited condition that affects the development of bones and teeth. HPP leads to defective mineralization—where bones are soft and prone to fractures—and premature tooth loss.
A Word From Verywell
Hypophosphatasia is a lifelong condition, and getting a diagnosis can be life-altering for the person affected and their family.
Support and advocacy groups can be a helpful way to connect with others living with HPP. Check online to research these groups, including at theNational Organization for Rare Disorderswebsite.
17 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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