Odontohypophosphatasia features early loss of “baby” teeth in infancy or early childhood, or unexpected loss of teeth sometime in adulthood. Here, the dental problems are an isolated finding without the characteristic bone problems of other forms of HPP.
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.
Mortality among patients with perinatal or infantile HPP has ranged from 58 to 100 percent within the first year of life.
Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The prevalence of severe forms of the disease has been estimated at 1/100 000.
Adult hypophosphatasia
Adult HPP may manifest with recurrent or slow-to-heal metatarsal fractures or subtrochanteric femoral pseudofractures. A review of Mayo Clinic patients diagnosed with HPP as adults demonstrated that nonspecific musculoskeletal complaints were common at the time of presentation.
Patients with childhood HPP typically survive, but many have chronic manifestations of disease. As previously noted, such manifestations may directly affect growth, mobility, and quality of life. Treatment therefore reflects this variation in disease.
In the U.S. and elsewhere, a diagnosis of HPP can be supported, but not made, by measuring the blood level of the form of vitamin B6 called pyridoxal 5ʹ-phosphate (PLP). This test is performed by several commercial laboratories. Individuals with HPP have elevated levels because PLP is normally broken down by TNSALP.
Memory. Vivid mental imagery as observed in hyperphantasia impacts people's ability to “mental time travel”, or the ability to remember past events as well as imagine future events. Hyperphantasics have reported more sensory details of episodic memories and future event constructions.
Low levels of ALP are less common. They may be a sign of a lack of zinc, malnutrition, pernicious anemia, thyroid disease, Wilson disease or hypophosphatasia, a rare genetic disease that affects bones and teeth. Learn more about laboratory tests, reference ranges, and understanding results.
Hypophosphatasia is a lifelong condition. It comes with many different symptoms and complications. Treatment for the condition requires a multidisciplinary team of specialists.
It's almost always fatal without treatment. But in another type, benign prenatal, bone problems that a doctor can see on an ultrasound get better on their own soon after the baby is born. Sometimes, people are genetic “carriers” of HPP, but don't have any symptoms.
Background. Hypophosphatasia (HPP) is a chronic, progressive bone mineralization disorder caused by loss-of-function variants in the ALPL gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP).
Hypophosphatasia (perinatal and infantile onset types) is a disabling condition on the Compassionate Allowance List, which qualifies an individual for an expedited approval process.
Diagnosis of HPP in Adults
Adults with HPP may come to clinical attention by finding low-serum ALP on routine laboratory testing or during the course of evaluation for osteoporosis or fractures.
This study shows that ALP mRNA and activity were significantly increased by ER stress in human primary VSMCs in vitro.
Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%. Conclusions: The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented.
Low ALP is rare. It wouldn't be unusual for a doctor to disregard a low ALP result. But if you have low ALP, you should be aware that in some people it is a sign of hypophosphatasia—HPP—a rare disease that affects bones and teeth.
High alkaline phosphatase (ALP) levels may indicate that there's damage to your liver or that you have a type of bone disorder. Liver damage creates a different type of ALP than bone disorders do.
The diet containing phosphorus, healthy fats, Zn, vitamin B12 and vitamin A can be started to increase alkaline phosphatase level.
Bone ALP regulates bone mineralization. It provides inorganic phosphate from pyrophosphate and phosphomonoesters and hydrolyzes pyrophosphate (mineralization inhibitor) for the hydroxyapatite synthesis [7,8].
Osteoporosis is a metabolic disease that raises alkaline phosphatase (ALP) levels. ALP, a homodimeric enzyme of 86 kilodaltons, plays a vital role in metabolism within the liver and bone. Clinicians use bisphosphonates to reduce the level of ALP, thus preventing a further decrease in bone mineral density.
In hypophosphatasia, mineralization is disrupted affecting a number of tissues, including bone and teeth. With X-linked hypophosphatemia, an inability of the cells in the body to properly process phosphate causes circulating levels of phosphate to be low, resulting in problems with bone and tooth development.
Hyperphosphatasia or hyperphosphatasaemia is an excess of alkaline phosphatase in the blood. It occurs in a syndrome known as osteoectasia with hyperphosphatasia, sometimes referred to as juvenile Paget's disease or hereditary hyperphosphatasia.
High ALP levels can be caused by bone diseases, such as Paget's disease, osteomalacia, rickets, bone tumors, or tumors that have spread from another part of the body to the bone, or by overactive parathyroid glands (hyperparathyroidism). Normal healing of a bone fracture can also raise ALP levels.