What is hypophosphatasia?
A rare, inherited condition that stops bones and teeth mineralising properly, and one that looks completely different from one person to the next.
An underactive enzyme
Hypophosphatasia is an inherited metabolic bone disease caused by loss-of-function variants in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase. Reduced activity of this enzyme leads to extracellular accumulation of its substrates, principally inorganic pyrophosphate, pyridoxal 5′-phosphate and phosphoethanolamine.
Inorganic pyrophosphate inhibits the formation of hydroxyapatite crystal. Its accumulation impairs mineralisation of bone and teeth, producing rickets in infants and children and osteomalacia in adults. Defective mineralisation of cementum results in premature loss of teeth with the root intact.
Pyridoxal 5′-phosphate, the circulating form of vitamin B6, is measurable in serum. Phosphoethanolamine is measurable in urine. Both are elevated in hypophosphatasia and support the biochemical diagnosis alongside a serum alkaline phosphatase activity that is persistently low for age and sex.
Clinical severity is highly variable. Reported presentations range from stillbirth with almost no skeletal mineralisation through to premature exfoliation of the primary teeth as the only manifestation. Six clinical forms are described: perinatal, benign prenatal, infantile, childhood, adult and odontohypophosphatasia.
The short version
- It is genetic. HPP is caused by changes in the ALPL gene and is present from conception.
- It is lifelong. Symptoms can ease and return, but the underlying condition does not go away.
- It is not contagious and nothing anyone did caused it.
- It is highly variable. Two people with the same genetic change can be affected very differently, even within one family.
- It is under-recognised. Mild forms are far more common than severe ones, and many go undiagnosed for decades.
- Low ALP is the clue. In almost every other bone disease ALP goes up. In HPP it goes down, which is exactly why it gets missed.
How HPP shows up across a lifetime
Nobody has all of these. What matters is the pattern, particularly when it sits alongside a persistently low ALP result.
Before birth to 6 months
- Bones that appear poorly mineralised on scans or X-rays
- A soft, narrow chest causing breathing difficulty
- Feeding problems and failure to gain weight
- Floppiness (low muscle tone) and delayed milestones
- Seizures that respond to vitamin B6
- High blood calcium, and calcium deposits in the kidneys
- Skull sutures that fuse too early, raising pressure inside the head
- Bowed or deformed limbs; blue-tinged whites of the eyes
6 months to adolescence
- Baby teeth lost before age five with the root still attached, usually the bottom front teeth first, and usually painless
- Bowed legs or knock knees
- Short stature and a waddling walk
- Delayed walking; tiring quickly; muscle weakness
- Bone and joint pain, sometimes dismissed as growing pains
- Fractures from minor knocks
- Rickets-like changes on X-ray despite normal calcium and vitamin D
Adulthood, often from middle age
- Repeated stress fractures in the feet that heal slowly or not at all
- Thigh-bone fractures and pseudofractures
- Chronic, deep bone and muscle pain
- Weakness in the hips and shoulders; difficulty with stairs
- Adult teeth loosening or falling out without gum disease
- Painful joint attacks from calcium crystal deposits (pseudogout)
- Persistent fatigue that limits daily life
Odontohypophosphatasia: when only the teeth are affected
Some people have HPP that shows up in the teeth alone, with no bone changes on imaging at all. It is thought to be the mildest and possibly the most common form. Early tooth loss with intact roots is worth investigating even when everything else seems fine.
The six recognised forms
Broadly, the earlier symptoms begin, the more severe the condition tends to be. Naming the form matters in Australia, because treatment funding currently depends on it.
Perinatal (severe)
Present before or at birth. Profound lack of bone mineralisation, deformed limbs, and a chest too soft to support breathing. Historically this form was usually fatal in early infancy; enzyme replacement therapy has changed survival substantially.
Perinatal benign
Bowing and poor mineralisation seen on prenatal scans that then improves on its own after birth, settling into one of the milder forms. Distinguishing this from the severe perinatal form is critical, because the outlook is completely different.
Infantile
Begins in the first six months. Poor weight gain, floppiness, rickets-like bone changes, breathing difficulty, high blood calcium and vitamin B6-responsive seizures. This is the form, together with perinatal HPP, that Australia currently funds treatment for.
Childhood (juvenile)
Begins after six months. Ranges from early tooth loss and low bone density through to rickets, bowed legs, short stature, fractures and a waddling gait. Symptoms often appear to settle when growth finishes, then return in adulthood.
Adult
Usually recognised in middle age. Recurrent foot stress fractures, thigh-bone pseudofractures, osteomalacia, chronic pain, muscle weakness, early adult tooth loss and calcium crystal arthritis. Frequently misdiagnosed for years.
Odontohypophosphatasia
Dental disease only, meaning premature tooth loss and severe decay, with no detectable bone involvement. The mildest form, and probably the most common.
How HPP is inherited
Everyone has two copies of the ALPL gene, one from each parent. HPP happens when one or both copies carry a change that reduces how well the enzyme works.
The severe forms are usually recessive. Both copies are affected, meaning both parents carry a change without necessarily having symptoms. Where both parents are carriers, each pregnancy carries roughly a one-in-four chance of a child being affected.
The milder forms are often dominant. A single altered copy can be enough, because the faulty version interferes with the working one. A parent with this pattern has about a one-in-two chance of passing the change to each child.
This is why mild HPP so often runs quietly through a family for generations before anyone names it: an aunt who lost her teeth young, a grandfather with unexplained foot fractures.
What families most often ask
If I have HPP, will my children?
It depends on the pattern in your family and on your partner's genetics. The honest answer is that this needs a genetic counsellor who can look at your specific results. It is not something to work out from a website. Referral is usually through your GP or specialist.
My relative has HPP. Should I be tested?
A simple blood test for alkaline phosphatase is a reasonable first step for close relatives, and it is inexpensive. If it comes back persistently low, that is the point to ask for further assessment.
Can two people with the same gene change be affected differently?
Yes, and often markedly. Siblings carrying identical changes can have very different severity, so a genetic result alone does not predict how someone's life will go.
Does “carrier” mean unaffected?
Not always. Some people with a single altered copy have no symptoms at all; others have real bone or dental problems. Being described as a carrier does not automatically mean you are in the clear.
Is testing before or during pregnancy possible?
Where the specific family gene change is already known, prenatal and pre-implantation testing options exist. A clinical genetics service can explain what is available and what it involves.
How many Australians have HPP? Nobody knows.
There has never been an Australian study of how common hypophosphatasia is. Every figure quoted here, including on this site, is drawn from overseas research, mostly European, and applied to an Australian population.
Internationally, the severe forms are estimated at roughly one in 300,000 people. Milder forms are believed to be considerably more common, and a large share are never diagnosed. When the Australian Government assessed funding for enzyme replacement therapy, it used an overseas-derived estimate of about 3.4 cases per million births for the most severe group.
That gap is not academic. Without local data it is harder to argue for funding, harder to plan services, and harder to convince clinicians that the condition is worth thinking of.
Building an accurate picture of who is living with HPP in Australia is one of the reasons Soft Bones Australia exists.
What HPP is often mistaken for
Adults with HPP frequently collect other labels first. If any of these were given to you and your alkaline phosphatase has been low, it is reasonable to ask the question.
Osteoporosis
The overlap is real: fractures, bone pain, low bone density. The distinguishing feature is the ALP result, which is high or normal in osteoporosis and low in HPP.
Osteogenesis imperfecta
Brittle bone disease shares the fracture pattern in children, but is a different condition with different genetics and different treatment.
Rickets from vitamin D deficiency
Looks similar on X-ray. The difference is in the bloods: in HPP, calcium and phosphate are normal or high rather than low.
Fibromyalgia
Widespread pain, fatigue and years without answers is a familiar story for adults with HPP. Some researchers suspect HPP is under-recognised in this group.
Arthritis and “wear and tear”
Calcium crystal deposits in the joints cause genuine arthritis-like attacks, which can become the diagnosis rather than a clue to the one underneath.
Growing pains
Children's bone pain is easily attributed to growth. Where it comes with early tooth loss or an odd gait, it deserves a closer look.
An important note on proportion
HPP is genuinely rare. A single low alkaline phosphatase result has many more common explanations, including some medications, an underactive thyroid, coeliac disease, and zinc or magnesium deficiency. Most people with a low ALP do not have HPP. The point is not to assume it, but to make sure someone checks.
Reviewed August 2026. This page is general information drawn from international clinical literature and is not medical advice. It has not yet been reviewed by a clinician on behalf of Soft Bones Australia.
How Soft Bones began
Soft Bones was founded in the United States in 2009 by Deborah Sittig, after her son Cannon was diagnosed with hypophosphatasia. At the time she could find almost no information or support, so she set out to build both, for her own family and for others facing the same diagnosis.
What began as one parents search for answers has grown into Soft Bones Inc, a US charity supporting people with HPP and the clinicians and researchers who care for them. Soft Bones Australia was established to bring that same information, support and community to Australians living with HPP.
Deborah Sittig, founder of Soft Bones
What is hypophosphatasia?
A rare, inherited condition that stops bones and teeth mineralising properly, and one that looks completely different from one person to the next.
An underactive enzyme
Hypophosphatasia is an inherited metabolic bone disease caused by loss-of-function variants in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase. Reduced activity of this enzyme leads to extracellular accumulation of its substrates, principally inorganic pyrophosphate, pyridoxal 5′-phosphate and phosphoethanolamine.
Inorganic pyrophosphate inhibits the formation of hydroxyapatite crystal. Its accumulation impairs mineralisation of bone and teeth, producing rickets in infants and children and osteomalacia in adults. Defective mineralisation of cementum results in premature loss of teeth with the root intact.
Pyridoxal 5′-phosphate, the circulating form of vitamin B6, is measurable in serum. Phosphoethanolamine is measurable in urine. Both are elevated in hypophosphatasia and support the biochemical diagnosis alongside a serum alkaline phosphatase activity that is persistently low for age and sex.
Clinical severity is highly variable. Reported presentations range from stillbirth with almost no skeletal mineralisation through to premature exfoliation of the primary teeth as the only manifestation. Six clinical forms are described: perinatal, benign prenatal, infantile, childhood, adult and odontohypophosphatasia.
The short version
- It is genetic. HPP is caused by changes in the ALPL gene and is present from conception.
- It is lifelong. Symptoms can ease and return, but the underlying condition does not go away.
- It is not contagious and nothing anyone did caused it.
- It is highly variable. Two people with the same genetic change can be affected very differently, even within one family.
- It is under-recognised. Mild forms are far more common than severe ones, and many go undiagnosed for decades.
- Low ALP is the clue. In almost every other bone disease ALP goes up. In HPP it goes down, which is exactly why it gets missed.
How HPP shows up across a lifetime
Nobody has all of these. What matters is the pattern, particularly when it sits alongside a persistently low ALP result.
Before birth to 6 months
- Bones that appear poorly mineralised on scans or X-rays
- A soft, narrow chest causing breathing difficulty
- Feeding problems and failure to gain weight
- Floppiness (low muscle tone) and delayed milestones
- Seizures that respond to vitamin B6
- High blood calcium, and calcium deposits in the kidneys
- Skull sutures that fuse too early, raising pressure inside the head
- Bowed or deformed limbs; blue-tinged whites of the eyes
6 months to adolescence
- Baby teeth lost before age five with the root still attached, usually the bottom front teeth first, and usually painless
- Bowed legs or knock knees
- Short stature and a waddling walk
- Delayed walking; tiring quickly; muscle weakness
- Bone and joint pain, sometimes dismissed as growing pains
- Fractures from minor knocks
- Rickets-like changes on X-ray despite normal calcium and vitamin D
Adulthood, often from middle age
- Repeated stress fractures in the feet that heal slowly or not at all
- Thigh-bone fractures and pseudofractures
- Chronic, deep bone and muscle pain
- Weakness in the hips and shoulders; difficulty with stairs
- Adult teeth loosening or falling out without gum disease
- Painful joint attacks from calcium crystal deposits (pseudogout)
- Persistent fatigue that limits daily life
Odontohypophosphatasia: when only the teeth are affected
Some people have HPP that shows up in the teeth alone, with no bone changes on imaging at all. It is thought to be the mildest and possibly the most common form. Early tooth loss with intact roots is worth investigating even when everything else seems fine.
The six recognised forms
Broadly, the earlier symptoms begin, the more severe the condition tends to be. Naming the form matters in Australia, because treatment funding currently depends on it.
Perinatal (severe)
Present before or at birth. Profound lack of bone mineralisation, deformed limbs, and a chest too soft to support breathing. Historically this form was usually fatal in early infancy; enzyme replacement therapy has changed survival substantially.
Perinatal benign
Bowing and poor mineralisation seen on prenatal scans that then improves on its own after birth, settling into one of the milder forms. Distinguishing this from the severe perinatal form is critical, because the outlook is completely different.
Infantile
Begins in the first six months. Poor weight gain, floppiness, rickets-like bone changes, breathing difficulty, high blood calcium and vitamin B6-responsive seizures. This is the form, together with perinatal HPP, that Australia currently funds treatment for.
Childhood (juvenile)
Begins after six months. Ranges from early tooth loss and low bone density through to rickets, bowed legs, short stature, fractures and a waddling gait. Symptoms often appear to settle when growth finishes, then return in adulthood.
Adult
Usually recognised in middle age. Recurrent foot stress fractures, thigh-bone pseudofractures, osteomalacia, chronic pain, muscle weakness, early adult tooth loss and calcium crystal arthritis. Frequently misdiagnosed for years.
Odontohypophosphatasia
Dental disease only, meaning premature tooth loss and severe decay, with no detectable bone involvement. The mildest form, and probably the most common.
How HPP is inherited
Everyone has two copies of the ALPL gene, one from each parent. HPP happens when one or both copies carry a change that reduces how well the enzyme works.
The severe forms are usually recessive. Both copies are affected, meaning both parents carry a change without necessarily having symptoms. Where both parents are carriers, each pregnancy carries roughly a one-in-four chance of a child being affected.
The milder forms are often dominant. A single altered copy can be enough, because the faulty version interferes with the working one. A parent with this pattern has about a one-in-two chance of passing the change to each child.
This is why mild HPP so often runs quietly through a family for generations before anyone names it: an aunt who lost her teeth young, a grandfather with unexplained foot fractures.
What families most often ask
If I have HPP, will my children?
It depends on the pattern in your family and on your partner's genetics. The honest answer is that this needs a genetic counsellor who can look at your specific results. It is not something to work out from a website. Referral is usually through your GP or specialist.
My relative has HPP. Should I be tested?
A simple blood test for alkaline phosphatase is a reasonable first step for close relatives, and it is inexpensive. If it comes back persistently low, that is the point to ask for further assessment.
Can two people with the same gene change be affected differently?
Yes, and often markedly. Siblings carrying identical changes can have very different severity, so a genetic result alone does not predict how someone's life will go.
Does “carrier” mean unaffected?
Not always. Some people with a single altered copy have no symptoms at all; others have real bone or dental problems. Being described as a carrier does not automatically mean you are in the clear.
Is testing before or during pregnancy possible?
Where the specific family gene change is already known, prenatal and pre-implantation testing options exist. A clinical genetics service can explain what is available and what it involves.
How many Australians have HPP? Nobody knows.
There has never been an Australian study of how common hypophosphatasia is. Every figure quoted here, including on this site, is drawn from overseas research, mostly European, and applied to an Australian population.
Internationally, the severe forms are estimated at roughly one in 300,000 people. Milder forms are believed to be considerably more common, and a large share are never diagnosed. When the Australian Government assessed funding for enzyme replacement therapy, it used an overseas-derived estimate of about 3.4 cases per million births for the most severe group.
That gap is not academic. Without local data it is harder to argue for funding, harder to plan services, and harder to convince clinicians that the condition is worth thinking of.
Building an accurate picture of who is living with HPP in Australia is one of the reasons Soft Bones Australia exists.
What HPP is often mistaken for
Adults with HPP frequently collect other labels first. If any of these were given to you and your alkaline phosphatase has been low, it is reasonable to ask the question.
Osteoporosis
The overlap is real: fractures, bone pain, low bone density. The distinguishing feature is the ALP result, which is high or normal in osteoporosis and low in HPP.
Osteogenesis imperfecta
Brittle bone disease shares the fracture pattern in children, but is a different condition with different genetics and different treatment.
Rickets from vitamin D deficiency
Looks similar on X-ray. The difference is in the bloods: in HPP, calcium and phosphate are normal or high rather than low.
Fibromyalgia
Widespread pain, fatigue and years without answers is a familiar story for adults with HPP. Some researchers suspect HPP is under-recognised in this group.
Arthritis and “wear and tear”
Calcium crystal deposits in the joints cause genuine arthritis-like attacks, which can become the diagnosis rather than a clue to the one underneath.
Growing pains
Children's bone pain is easily attributed to growth. Where it comes with early tooth loss or an odd gait, it deserves a closer look.
An important note on proportion
HPP is genuinely rare. A single low alkaline phosphatase result has many more common explanations, including some medications, an underactive thyroid, coeliac disease, and zinc or magnesium deficiency. Most people with a low ALP do not have HPP. The point is not to assume it, but to make sure someone checks.
Reviewed August 2026. This page is general information drawn from international clinical literature and is not medical advice. It has not yet been reviewed by a clinician on behalf of Soft Bones Australia.