Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report
Abstract Background Hypophosphatasia is an inherited bone disease characterized by low alkaline phosphatase activity encoded by ALPL. Clinically, hypophosphatasia can be categorized as perinatal, infantile, childhood, and adult forms, as well as odonto-hypophosphatasia, according to the age at first...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | Journal of Medical Case Reports |
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| Online Access: | http://link.springer.com/article/10.1186/s13256-019-2045-4 |
| _version_ | 1818842723444064256 |
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| author | Kazunori Fukushima Keiko Kawai-Kowase Yukio Yonemoto Makoto Fujiwara Hiroko Sato Mahito Sato Takuo Kubota Keiichi Ozono Junich Tamura |
| author_facet | Kazunori Fukushima Keiko Kawai-Kowase Yukio Yonemoto Makoto Fujiwara Hiroko Sato Mahito Sato Takuo Kubota Keiichi Ozono Junich Tamura |
| author_sort | Kazunori Fukushima |
| collection | DOAJ |
| description | Abstract Background Hypophosphatasia is an inherited bone disease characterized by low alkaline phosphatase activity encoded by ALPL. Clinically, hypophosphatasia can be categorized as perinatal, infantile, childhood, and adult forms, as well as odonto-hypophosphatasia, according to the age at first sign or dental manifestations. Adult hypophosphatasia typically presents in middle-aged patients who appear to be in good health in early adulthood and manifests as painful feet caused by recurrent, slow-healing stress fractures of the lower limb. Because the symptoms of adult hypophosphatasia vary and are common, many patients with hypophosphatasia might be not diagnosed accurately and thus may receive inappropriate treatment. Case presentation We report a case of a 35-year-old Japanese woman with low serum alkaline phosphatase detected at a routine medical checkup. She had mild muscle/bone pain but no history of rickets, fractures, or dental problems. Measurement of bone mineral density of the lumbar spine and the femoral neck revealed osteopenia below the expected range for age in a young adult. Abdominal ultrasonography revealed numerous microcalcifications in both kidneys. Analysis of amino acids in urine revealed that phosphoethanolamine was elevated. Low serum alkaline phosphatase activity, elevation of phosphoethanolamine, and low bone mineral density supported the diagnosis of hypophosphatasia. ALPL mutation analysis revealed two mutations: p.Phe327Leu and c.1559delT. These genetic abnormalities were previously reported in perinatal, infantile, and childhood but not adult hypophosphatasia. On the basis of the clinical presentation, laboratory and imaging findings, and genetic analyses, the patient was definitively diagnosed with adult hypophosphatasia. To the best of our knowledge, this is the first case report of adult hypophosphatasia with the compound heterozygous mutations p.Phe327Leu and c.1559delT. Conclusions Although the risk of bone fracture was high in this case, treatment approaches differ between osteoporosis and hypophosphatasia. Because adult hypophosphatasia diagnosis is often difficult because of their varied symptoms, hypophosphatasia should be considered in the differential diagnosis of low serum alkaline phosphatase. Early diagnosis is important so that appropriate treatment can be initiated. |
| first_indexed | 2024-12-19T04:46:30Z |
| format | Article |
| id | doaj.art-0f6c85a1e6274fb886e71a94995499c4 |
| institution | Directory Open Access Journal |
| issn | 1752-1947 |
| language | English |
| last_indexed | 2024-12-19T04:46:30Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Medical Case Reports |
| spelling | doaj.art-0f6c85a1e6274fb886e71a94995499c42022-12-21T20:35:27ZengBMCJournal of Medical Case Reports1752-19472019-04-011311610.1186/s13256-019-2045-4Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case reportKazunori Fukushima0Keiko Kawai-Kowase1Yukio Yonemoto2Makoto Fujiwara3Hiroko Sato4Mahito Sato5Takuo Kubota6Keiichi Ozono7Junich Tamura8Department of Emergency Medicine, Gunma University Graduate School of MedicineDepartment of General Medicine, Gunma University Graduate School of MedicineDepartment of Orthopedic Surgery, Gunma University Graduate School of MedicineDepartment of Pediatrics, Osaka University Graduate School of MedicineDepartment of General Medicine, Gunma University Graduate School of MedicineDepartment of General Medicine, Gunma University Graduate School of MedicineDepartment of Pediatrics, Osaka University Graduate School of MedicineDepartment of Pediatrics, Osaka University Graduate School of MedicineDepartment of General Medicine, Gunma University Graduate School of MedicineAbstract Background Hypophosphatasia is an inherited bone disease characterized by low alkaline phosphatase activity encoded by ALPL. Clinically, hypophosphatasia can be categorized as perinatal, infantile, childhood, and adult forms, as well as odonto-hypophosphatasia, according to the age at first sign or dental manifestations. Adult hypophosphatasia typically presents in middle-aged patients who appear to be in good health in early adulthood and manifests as painful feet caused by recurrent, slow-healing stress fractures of the lower limb. Because the symptoms of adult hypophosphatasia vary and are common, many patients with hypophosphatasia might be not diagnosed accurately and thus may receive inappropriate treatment. Case presentation We report a case of a 35-year-old Japanese woman with low serum alkaline phosphatase detected at a routine medical checkup. She had mild muscle/bone pain but no history of rickets, fractures, or dental problems. Measurement of bone mineral density of the lumbar spine and the femoral neck revealed osteopenia below the expected range for age in a young adult. Abdominal ultrasonography revealed numerous microcalcifications in both kidneys. Analysis of amino acids in urine revealed that phosphoethanolamine was elevated. Low serum alkaline phosphatase activity, elevation of phosphoethanolamine, and low bone mineral density supported the diagnosis of hypophosphatasia. ALPL mutation analysis revealed two mutations: p.Phe327Leu and c.1559delT. These genetic abnormalities were previously reported in perinatal, infantile, and childhood but not adult hypophosphatasia. On the basis of the clinical presentation, laboratory and imaging findings, and genetic analyses, the patient was definitively diagnosed with adult hypophosphatasia. To the best of our knowledge, this is the first case report of adult hypophosphatasia with the compound heterozygous mutations p.Phe327Leu and c.1559delT. Conclusions Although the risk of bone fracture was high in this case, treatment approaches differ between osteoporosis and hypophosphatasia. Because adult hypophosphatasia diagnosis is often difficult because of their varied symptoms, hypophosphatasia should be considered in the differential diagnosis of low serum alkaline phosphatase. Early diagnosis is important so that appropriate treatment can be initiated.http://link.springer.com/article/10.1186/s13256-019-2045-4HypophosphatasiaAlkaline phosphataseCompound heterozygous mutationMedical checkupOsteoporosis |
| spellingShingle | Kazunori Fukushima Keiko Kawai-Kowase Yukio Yonemoto Makoto Fujiwara Hiroko Sato Mahito Sato Takuo Kubota Keiichi Ozono Junich Tamura Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report Journal of Medical Case Reports Hypophosphatasia Alkaline phosphatase Compound heterozygous mutation Medical checkup Osteoporosis |
| title | Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report |
| title_full | Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report |
| title_fullStr | Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report |
| title_full_unstemmed | Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report |
| title_short | Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report |
| title_sort | adult hypophosphatasia with compound heterozygous p phe327leu missense and c 1559delt frameshift mutations in tissue nonspecific alkaline phosphatase gene a case report |
| topic | Hypophosphatasia Alkaline phosphatase Compound heterozygous mutation Medical checkup Osteoporosis |
| url | http://link.springer.com/article/10.1186/s13256-019-2045-4 |
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