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What Is Alkaline Phosphatase? What Are the Symptoms of Low ALP?

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What Is Alkaline Phosphatase? What Are the Symptoms of Low ALP? What is the treatment for HPP? In 2015, asfotase alfa (Strensiq™) was approved for use in the US, the European Union, and Canada for pediatric-onset HPP, and in Japan for HPP with onset at any age. The medication is an injection given multiple times per week underneath the skin (subcutaneous). It is a recombinant (factory-made) form of ALP that has a bone-targeting component. When patients take asfotase alfa, ALP levels measured in the blood are quite high (often in the multiple thousands). Therefore, measuring ALP levels is typically not helpful once a patient is on therapy. What is Alkaline Phosphatase? What are the symptoms of low ALP? For more information, please contact Patients with hypophosphatasia (HPP) have Low ALP can lead to multiple symptoms of HPP, the Soft Bones Foundation. a low blood alkaline phosphatase (ALP) level. including poor bone mineralization and rickets as well (866) 827-9937 – Toll Free as early tooth loss (prior to age 5 years). It is also (973) 453-3093 – Direct Line thought that PPi may build up in muscle tissue 121 Hawkins Place, #267 ALP is an enzyme (a protein that breaks down and may be responsible for the pain and muscle Boonton, New Jersey 07005 chemicals). Most health providers are aware that weakness that some patients with HPP experience. www.SoftBones.org high ALP levels may indicate medical problems, such as liver disease or other bone diseases besides HPP, but many providers may not recognize that low ALP levels can indicate HPP. Low ALP is important What questions should patients ask Written by because the inability to break down chemicals can their doctors about ALP? Jill Simmons, MD lead to elevated levels of these chemicals, which Associate Professor of Pediatrics, Ian Burr Division can cause multiple problems. of Pediatric Endocrinology and Diabetes, The result of low ALP is similar to the result that a It is important to make certain that a patient’s ALP Vanderbilt University Medical Center Director, Program for Pediatric Metabolic Bone Disease vehicular accident has upon traffi c; if there is a block in level is being measured by a lab that has age- and the road due to an accident, then the cars trying to go gender-appropriate normal values. This publication is distributed by Soft Bones Inc., in that direction cannot move forward and the volume The U.S. Hypophosphatasia Foundation. of cars on the road before the accident increases. © Soft Bones Inc. 2017. All Rights Reserved. Similarly, without ALP, certain chemicals cannot be the highest levels occur during infancy and early to measurement. Testing for the other chemicals that broken down and instead increase. These chemicals adolescence. Some labs only report adult normal values; are typically broken down by ALP (PPi, PEA) is more include vitamin B6 (pyridoxal 5' phosphate, PLP), therefore, children who have low ALP levels may be expensive and technically difficult as well as less precise, pyrophosphate (PPi) and phosphoethanolamine (PEA). missed, as their levels might appear to be normal and this testing is therefore not typically performed Elevation of PLP and PPi are thought to cause many using an adult reference range but are actually low in the US. of the symptoms of HPP. for that child’s age. It is important to be certain that a patient’s blood is being sent to a lab that has age- and gender-adjusted normal ranges reported. What happens when PPi and What lab tests are important? vitamin B6 are elevated in the blood? Once it is certain that an ALP level is low, other tests are In HPP, blood ALP levels are low. ALP is often measured typically needed because low ALP levels do not always on routine blood biochemical panels. There are multiple indicate HPP. In the United States, measurement of the In bone tissue, pyrophosphate (PPi) is converted to forms of ALP, but the one that is important for HPP is blood level of vitamin B6 (PLP) is generally obtained. In phosphorus by ALP. Phosphorus then combines with tissue non-specific ALP (TNSALP). This form is measured patients with HPP, vitamin B6 (PLP) is elevated. The level calcium to form mineralized bone tissue. As PPi in these routine panels. Normal blood ALP levels vary of vitamin B6 can be affected by vitamin supplementation levels inhibit the formation of bone tissue, an increase between patients based upon age and gender. Children with vitamin B6, so it is important to avoid vitamin in PPi leads to poor bone mineralization, and therefore have higher levels than adults, and during childhood, B6-containing supplements for at least one week prior the abnormal bone findings that occur in patients with HPP. These elevated PPi levels also inhibit the formation of normal cementum, which is necessary » AGE- AND GENDER-ADJUSTED ALP REFERENCE RANGES to keep teeth attached to the jaw. Suspicion of HPP On the surface of the brain at the blood/ brain barrier, <1 month 60 320 ALP converts a form of vitamin B6 (pyridoxal 5’ Normal age-adjusted ALP 1–11 months 70 350 phosphate) to another form of vitamin B6 (pyridoxal) 1–3 years 125 320 so that it can cross into the brain and help to form 4–6 years 150 370 neurotransmitters in the brain. Without these 7–9 years 150 440 neurotransmitters, seizures can occur. These seizures 10–11 years (M) 150 470 only occur in the infantile form of HPP, and fortunately do not occur in all patients with the infantile form. There 10–11 years (F) 150 530 is no clear evidence that there are neurologic problems 12–13 years (M) 160 500 in older patients with HPP. 12–13 years (F) 110 525 14–15 years (M) 130 530 AGE, MALE (M)/FEMALE (F) AGE, 14–15 years (F) 55 305 16–19 years (M) 60 270 16–19 years (F) 40 120 ≥20 years 40 120 0 100 200 300 400 500 600 ALP ACTIVITY (U/L) What is the treatment for HPP? In 2015, asfotase alfa (Strensiq™) was approved for use in the US, the European Union, and Canada for pediatric-onset HPP, and in Japan for HPP with onset at any age. The medication is an injection given multiple times per week underneath the skin (subcutaneous). It is a recombinant (factory-made) form of ALP that has a bone-targeting component. When patients take asfotase alfa, ALP levels measured in the blood are quite high (often in the multiple thousands). Therefore, measuring ALP levels is typically not helpful once a patient is on therapy. What is Alkaline Phosphatase? What are the symptoms of low ALP? For more information, please contact Patients with hypophosphatasia (HPP) have Low ALP can lead to multiple symptoms of HPP, the Soft Bones Foundation. a low blood alkaline phosphatase (ALP) level. including poor bone mineralization and rickets as well (866) 827-9937 – Toll Free as early tooth loss (prior to age 5 years). It is also (973) 453-3093 – Direct Line thought that PPi may build up in muscle tissue 121 Hawkins Place, #267 ALP is an enzyme (a protein that breaks down and may be responsible for the pain and muscle Boonton, New Jersey 07005 chemicals). Most health providers are aware that weakness that some patients with HPP experience. www.SoftBones.org high ALP levels may indicate medical problems, such as liver disease or other bone diseases besides HPP, but many providers may not recognize that low ALP levels can indicate HPP. Low ALP is important What questions should patients ask Written by because the inability to break down chemicals can their doctors about ALP? Jill Simmons, MD lead to elevated levels of these chemicals, which Associate Professor of Pediatrics, Ian Burr Division can cause multiple problems. of Pediatric Endocrinology and Diabetes, The result of low ALP is similar to the result that a It is important to make certain that a patient’s ALP Vanderbilt University Medical Center Director, Program for Pediatric Metabolic Bone Disease vehicular accident has upon traffi c; if there is a block in level is being measured by a lab that has age- and the road due to an accident, then the cars trying to go gender-appropriate normal values. This publication is distributed by Soft Bones Inc., in that direction cannot move forward and the volume The U.S. Hypophosphatasia Foundation. of cars on the road before the accident increases. © Soft Bones Inc. 2017. All Rights Reserved..
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