Adult hypophosphatasia presenting with recurrent acute joint pain
Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with sympt...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2025-01-01
|
| Series: | Endocrinology, Diabetes & Metabolism Case Reports |
| Subjects: | |
| Online Access: | https://edm.bioscientifica.com/view/journals/edm/2025/1/EDM-24-0121.xml |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832539712333545472 |
|---|---|
| author | Hayao Yoshida Takaaki Murakami Atsubumi Ogawa Takashi Sunouchi Naoko Hidaka Nobuaki Ito Hiromi Murakami Hidenori Kawasaki Tomoyuki Akiyama Katsumi Nakajima Daisuke Yabe Taizo Yamamoto |
| author_facet | Hayao Yoshida Takaaki Murakami Atsubumi Ogawa Takashi Sunouchi Naoko Hidaka Nobuaki Ito Hiromi Murakami Hidenori Kawasaki Tomoyuki Akiyama Katsumi Nakajima Daisuke Yabe Taizo Yamamoto |
| author_sort | Hayao Yoshida |
| collection | DOAJ |
| description | Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. |
| format | Article |
| id | doaj-art-ce4b7ce34f9248738f4a03f7a90ae8ba |
| institution | Kabale University |
| issn | 2052-0573 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism Case Reports |
| spelling | doaj-art-ce4b7ce34f9248738f4a03f7a90ae8ba2025-02-05T10:18:10ZengBioscientificaEndocrinology, Diabetes & Metabolism Case Reports2052-05732025-01-012025110.1530/EDM-24-01211Adult hypophosphatasia presenting with recurrent acute joint painHayao Yoshida0Takaaki Murakami1Atsubumi Ogawa2Takashi Sunouchi3Naoko Hidaka4Nobuaki Ito5Hiromi Murakami6Hidenori Kawasaki7Tomoyuki Akiyama8Katsumi Nakajima9Daisuke Yabe10Taizo Yamamoto11Department of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, JapanDepartment of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, JapanDepartment of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, JapanDivision of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, JapanDivision of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, JapanOsteoporosis Center, The University of Tokyo Hospital, Tokyo, JapanDepartment of Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, JapanDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, JapanHypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms.https://edm.bioscientifica.com/view/journals/edm/2025/1/EDM-24-0121.xmlhypophosphatasiagenetic disordersbone |
| spellingShingle | Hayao Yoshida Takaaki Murakami Atsubumi Ogawa Takashi Sunouchi Naoko Hidaka Nobuaki Ito Hiromi Murakami Hidenori Kawasaki Tomoyuki Akiyama Katsumi Nakajima Daisuke Yabe Taizo Yamamoto Adult hypophosphatasia presenting with recurrent acute joint pain Endocrinology, Diabetes & Metabolism Case Reports hypophosphatasia genetic disorders bone |
| title | Adult hypophosphatasia presenting with recurrent acute joint pain |
| title_full | Adult hypophosphatasia presenting with recurrent acute joint pain |
| title_fullStr | Adult hypophosphatasia presenting with recurrent acute joint pain |
| title_full_unstemmed | Adult hypophosphatasia presenting with recurrent acute joint pain |
| title_short | Adult hypophosphatasia presenting with recurrent acute joint pain |
| title_sort | adult hypophosphatasia presenting with recurrent acute joint pain |
| topic | hypophosphatasia genetic disorders bone |
| url | https://edm.bioscientifica.com/view/journals/edm/2025/1/EDM-24-0121.xml |
| work_keys_str_mv | AT hayaoyoshida adulthypophosphatasiapresentingwithrecurrentacutejointpain AT takaakimurakami adulthypophosphatasiapresentingwithrecurrentacutejointpain AT atsubumiogawa adulthypophosphatasiapresentingwithrecurrentacutejointpain AT takashisunouchi adulthypophosphatasiapresentingwithrecurrentacutejointpain AT naokohidaka adulthypophosphatasiapresentingwithrecurrentacutejointpain AT nobuakiito adulthypophosphatasiapresentingwithrecurrentacutejointpain AT hiromimurakami adulthypophosphatasiapresentingwithrecurrentacutejointpain AT hidenorikawasaki adulthypophosphatasiapresentingwithrecurrentacutejointpain AT tomoyukiakiyama adulthypophosphatasiapresentingwithrecurrentacutejointpain AT katsuminakajima adulthypophosphatasiapresentingwithrecurrentacutejointpain AT daisukeyabe adulthypophosphatasiapresentingwithrecurrentacutejointpain AT taizoyamamoto adulthypophosphatasiapresentingwithrecurrentacutejointpain |