Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia
Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the ALPL gene encoding tissue non-specific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, ric...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Osteoporosis and Sarcopenia |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405525523001152 |
| _version_ | 1797317431824220160 |
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| author | Se-Min Kim Funda Korkmaz Steve Sims Vitaly Ryu Tony Yuen Mone Zaidi |
| author_facet | Se-Min Kim Funda Korkmaz Steve Sims Vitaly Ryu Tony Yuen Mone Zaidi |
| author_sort | Se-Min Kim |
| collection | DOAJ |
| description | Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the ALPL gene encoding tissue non-specific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, rickets, and multiple radiographic fractures, and died shortly after of epileptic seizure and respiratory distress. The term “hypophosphatasia” was coined as the patients’ alkaline phosphatase levels were significantly low. Since then, our understanding of HPP has evolved, and now we appreciate causative genetic mutation and the broad spectrum of clinical presentation depending on the age of onset, severity, and skeletal involvement: perinatal, infantile, childhood, adult and odontohypophosphatasia. The new development of enzyme replacement with asfostase alfa has saved the lives of severe form of hypophosphatasia. However, it is still unclear and remains challenging how to manage adult HPP that often presents with mild and non-specific symptoms such as muscle pain, joint stiffness, fatigue, anxiety, or low bone mass, which are common in the general population and not necessarily attributed to HPP. In this review, we will present 3 unique cases of adult HPP and discuss the pathophysiology, clinical presentation particularly neuromuscular and neurocognitive symptoms and management of adult HPP. |
| first_indexed | 2024-03-08T03:34:50Z |
| format | Article |
| id | doaj.art-16c06350067c4feaabe7803a5d555ffa |
| institution | Directory Open Access Journal |
| issn | 2405-5255 |
| language | English |
| last_indexed | 2024-03-08T03:34:50Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Osteoporosis and Sarcopenia |
| spelling | doaj.art-16c06350067c4feaabe7803a5d555ffa2024-02-10T04:44:45ZengElsevierOsteoporosis and Sarcopenia2405-52552023-12-0194115120Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasiaSe-Min Kim0Funda Korkmaz1Steve Sims2Vitaly Ryu3Tony Yuen4Mone Zaidi5Corresponding author. Center for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA.; Center for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USACenter for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USACenter for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USACenter for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USACenter for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USACenter for Translational Medicine and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, NY, USAHypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the ALPL gene encoding tissue non-specific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, rickets, and multiple radiographic fractures, and died shortly after of epileptic seizure and respiratory distress. The term “hypophosphatasia” was coined as the patients’ alkaline phosphatase levels were significantly low. Since then, our understanding of HPP has evolved, and now we appreciate causative genetic mutation and the broad spectrum of clinical presentation depending on the age of onset, severity, and skeletal involvement: perinatal, infantile, childhood, adult and odontohypophosphatasia. The new development of enzyme replacement with asfostase alfa has saved the lives of severe form of hypophosphatasia. However, it is still unclear and remains challenging how to manage adult HPP that often presents with mild and non-specific symptoms such as muscle pain, joint stiffness, fatigue, anxiety, or low bone mass, which are common in the general population and not necessarily attributed to HPP. In this review, we will present 3 unique cases of adult HPP and discuss the pathophysiology, clinical presentation particularly neuromuscular and neurocognitive symptoms and management of adult HPP.http://www.sciencedirect.com/science/article/pii/S2405525523001152 |
| spellingShingle | Se-Min Kim Funda Korkmaz Steve Sims Vitaly Ryu Tony Yuen Mone Zaidi Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia Osteoporosis and Sarcopenia |
| title | Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia |
| title_full | Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia |
| title_fullStr | Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia |
| title_full_unstemmed | Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia |
| title_short | Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia |
| title_sort | musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia |
| url | http://www.sciencedirect.com/science/article/pii/S2405525523001152 |
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