BACKGROUND Hypophosphatasia(HPP)is a rare metabolic disorder caused by low tissue-nonspecific alkaline phosphatase(ALP)activity,presenting symptoms from bone demineralization to tooth loss.It affects multiple systems ...BACKGROUND Hypophosphatasia(HPP)is a rare metabolic disorder caused by low tissue-nonspecific alkaline phosphatase(ALP)activity,presenting symptoms from bone demineralization to tooth loss.It affects multiple systems and is diagnosed based on clinical symptoms,radiological findings,and lab tests.This case report empha-sizes considering HPP in patients with unexplained bone pain and low ALP levels,especially with underlying osteopenia or osteoporosis.It highlights the importance of genetic testing and counseling for early diagnosis and treatment,aiming to raise clinician awareness.CASE SUMMARY We present a case of a 65-year-old female patient who was referred to our endoc-rinology clinic for complaints of generalized bone pain and hypothyroidism.Initial evaluation revealed osteopenia,managed with calcium and vitamin D supplementation.Persistently low ALP levels and elevated vitamin B6 levels led to the diagnosis of HPP,confirmed by genetic testing identifying a pathogenic ALPL gene variant[c.119C>T(p.Ala40Val)].Despite conservative treatment,her bone density declined,although remaining in the osteopenic range.The Fracture Risk Assessment score indicated a low risk of major osteoporotic and hip fractures,not warranting immediate treatment.Plans are underway to initiate enzyme replacement therapy with asfotase alfa.CONCLUSION Recognizing HPP is crucial,as early diagnosis and treatment can significantly improve patient outcomes and prevent complications.展开更多
Hypophosphatasia(HPP)is a rare metabolic bone disorder often misdiagnosed as fibromyalgia due to overlapping symptoms such as chronic pain,fatigue,and muscle weakness.This diagnostic error disproportionately affects w...Hypophosphatasia(HPP)is a rare metabolic bone disorder often misdiagnosed as fibromyalgia due to overlapping symptoms such as chronic pain,fatigue,and muscle weakness.This diagnostic error disproportionately affects women and can result in significant psychological distress due to repeated dismissal of symptoms.Despite low serum alkaline phosphatase(ALP)being a key biochemical clue to HPP,it is frequently overlooked in standard diagnostic evaluations.Consequen-tly,many patients endure years of ineffective treatment,invalidation,and worse-ning psychiatric outcomes.This editorial emphasizes the need for greater clinical vigilance in distinguishing HPP from fibromyalgia,particularly when features such as chronic pain,premature tooth loss,and persistently low ALP are present.Gender biases in pain diagnosis further compound this problem,leading to gr-eater misdiagnosis rates among women and contributing to the erosion of trust in medical care.The psychiatric consequences of diagnostic delays are substantial,with affected individuals experiencing elevated rates of depression,anxiety,and emotional distress.Greater recognition of low ALP as a meaningful diagnostic clue may enhance diagnostic accuracy,improve patient outcomes,and reduce the psychological toll of misdiagnosis.展开更多
Background: Alkaline phosphatase has 4 isozymes, tissue non-specific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), intestinal alkaline phosphatase and germ-cell alkaline phosphatase. Hypophosphat...Background: Alkaline phosphatase has 4 isozymes, tissue non-specific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), intestinal alkaline phosphatase and germ-cell alkaline phosphatase. Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutations of the gene encoding TNAP. Although TNAP is expressed in various tissues, the primary HPP symptoms appear in bones and teeth. The clinical severity of HPP varies widely from the most severe (perinatal, infantile and childhood) to the mildest forms (adult, and odonto-hypophosphatasia). We reported that gene therapy using a single injection of lentiviral vector expressing bone-targeted TNAP (TNAP-D10) is effective in preventing all the skeletal of HPP in TNAP knockout (Alpl–/–) mice as the model of infantile HPP. Objective: In this study we focus on evaluating the efficacy of treatment with gene therapy on the bone and teeth using TNAP-D10 and also we investigate the feasibility of gene therapy using bone-targeted PLAP (PLAP-D10). Methods and Findings: We used Alpl–/–mice that develop skeletal disease at postnatal days 6-8 mimicking the infantile form of human HPP. We injected 100 μl of lentiviral vectors harboring TNALP-D10 (5.0 × 107 TU) or PLAP-D10 (5.0 × 107 TU) to 1-day-old Alpl–/–?mice via the jugular vein. We performed histological analysis and micro-CT evaluation on bone and mandible of Alpl–/–?mice. The alveolar bone, enamel and dentin defects were corrected on treated Alpl–/–?mice by this treatment. Additionally the long bone growth rates (LGR) of long bones were encouraged on treated Alpl–/–?mice compared with untreated mice. Conclusions: These results indicate that the bone-targeted TNAP treatment mediated by lentivirus can correct not only the bone disorder but also the dental symptoms in Alpl–/–. This study also shows that PLAP-D10 can potentially be used to correct HPP disease.展开更多
Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutation of the gene encoding tissue non-specific alkaline phosphatase (TNSALP). Odonto-HPP is well known as the mildest of HPP. The manifestations inv...Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutation of the gene encoding tissue non-specific alkaline phosphatase (TNSALP). Odonto-HPP is well known as the mildest of HPP. The manifestations involve only the teeth, such as premature primary teeth exfoliation caused by reduction of alveolar bone, enlarged dental pulp chamber, and dental defects. We report a case of a 9-years-old boy who developed HPP. He was observed from the primary dentition to the mixed dentition period. At initial presentation at our hospital, he had multiple premature exfoliation of primary teeth and reduction of the alveolar bone. HPP was suspected due to the low level of ALP activity in serum, his oral manifestation, and dental history. He was referred to a physician for the final diagnosis. Therefore his compound heterozygote mutations, c.1559 delT (T/delT) and c.407G > A (G/A), were found in TNSALP and he diagnosed with odonto-HPP. Even though these mutations were reported as being involved in odonto-HPP, his mineral densities tended to be lower than that of his age. It is therefore necessary to investigate the bone mineralization level in odonto-HPP without other bone symptoms. Moreover, ongoing enzyme-replacement therapy in odonto-HPP might improve dental abnormality and bone disorders.展开更多
目的本研究旨在分析中国低磷酸酶血症患者的基因突变特点和常见就诊原因,提醒相关医生加以注意,以提高诊断效率。方法通过中国知网、维普中文科技期刊数据库、万方数据库、Pub Med、Ovid、Web of Science和Embase,检索截止到2015年12月3...目的本研究旨在分析中国低磷酸酶血症患者的基因突变特点和常见就诊原因,提醒相关医生加以注意,以提高诊断效率。方法通过中国知网、维普中文科技期刊数据库、万方数据库、Pub Med、Ovid、Web of Science和Embase,检索截止到2015年12月31日的可能包含低磷酸酶血症的病例的文献。根据纳入与排除标准进行筛选和评价,然后提取所纳入文献中的就诊信息,进行归纳和统计分析。结果最终筛选出25篇包含中国低磷酸酶血症患者就诊信息的文献,共包含34位患者。笔者发现ALPL基因突变主要分布在5、10号外显子,其中75.0%为错义突变。34位患者中16位(47%)因乳牙早失就诊,12位(35%)因骨骼异常就诊。结论中国HP患者ALPL基因突变在外显子上的分布不同于其他种族,乳牙早失和骨骼异常是常见就诊原因。展开更多
文摘BACKGROUND Hypophosphatasia(HPP)is a rare metabolic disorder caused by low tissue-nonspecific alkaline phosphatase(ALP)activity,presenting symptoms from bone demineralization to tooth loss.It affects multiple systems and is diagnosed based on clinical symptoms,radiological findings,and lab tests.This case report empha-sizes considering HPP in patients with unexplained bone pain and low ALP levels,especially with underlying osteopenia or osteoporosis.It highlights the importance of genetic testing and counseling for early diagnosis and treatment,aiming to raise clinician awareness.CASE SUMMARY We present a case of a 65-year-old female patient who was referred to our endoc-rinology clinic for complaints of generalized bone pain and hypothyroidism.Initial evaluation revealed osteopenia,managed with calcium and vitamin D supplementation.Persistently low ALP levels and elevated vitamin B6 levels led to the diagnosis of HPP,confirmed by genetic testing identifying a pathogenic ALPL gene variant[c.119C>T(p.Ala40Val)].Despite conservative treatment,her bone density declined,although remaining in the osteopenic range.The Fracture Risk Assessment score indicated a low risk of major osteoporotic and hip fractures,not warranting immediate treatment.Plans are underway to initiate enzyme replacement therapy with asfotase alfa.CONCLUSION Recognizing HPP is crucial,as early diagnosis and treatment can significantly improve patient outcomes and prevent complications.
文摘Hypophosphatasia(HPP)is a rare metabolic bone disorder often misdiagnosed as fibromyalgia due to overlapping symptoms such as chronic pain,fatigue,and muscle weakness.This diagnostic error disproportionately affects women and can result in significant psychological distress due to repeated dismissal of symptoms.Despite low serum alkaline phosphatase(ALP)being a key biochemical clue to HPP,it is frequently overlooked in standard diagnostic evaluations.Consequen-tly,many patients endure years of ineffective treatment,invalidation,and worse-ning psychiatric outcomes.This editorial emphasizes the need for greater clinical vigilance in distinguishing HPP from fibromyalgia,particularly when features such as chronic pain,premature tooth loss,and persistently low ALP are present.Gender biases in pain diagnosis further compound this problem,leading to gr-eater misdiagnosis rates among women and contributing to the erosion of trust in medical care.The psychiatric consequences of diagnostic delays are substantial,with affected individuals experiencing elevated rates of depression,anxiety,and emotional distress.Greater recognition of low ALP as a meaningful diagnostic clue may enhance diagnostic accuracy,improve patient outcomes,and reduce the psychological toll of misdiagnosis.
文摘Background: Alkaline phosphatase has 4 isozymes, tissue non-specific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), intestinal alkaline phosphatase and germ-cell alkaline phosphatase. Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutations of the gene encoding TNAP. Although TNAP is expressed in various tissues, the primary HPP symptoms appear in bones and teeth. The clinical severity of HPP varies widely from the most severe (perinatal, infantile and childhood) to the mildest forms (adult, and odonto-hypophosphatasia). We reported that gene therapy using a single injection of lentiviral vector expressing bone-targeted TNAP (TNAP-D10) is effective in preventing all the skeletal of HPP in TNAP knockout (Alpl–/–) mice as the model of infantile HPP. Objective: In this study we focus on evaluating the efficacy of treatment with gene therapy on the bone and teeth using TNAP-D10 and also we investigate the feasibility of gene therapy using bone-targeted PLAP (PLAP-D10). Methods and Findings: We used Alpl–/–mice that develop skeletal disease at postnatal days 6-8 mimicking the infantile form of human HPP. We injected 100 μl of lentiviral vectors harboring TNALP-D10 (5.0 × 107 TU) or PLAP-D10 (5.0 × 107 TU) to 1-day-old Alpl–/–?mice via the jugular vein. We performed histological analysis and micro-CT evaluation on bone and mandible of Alpl–/–?mice. The alveolar bone, enamel and dentin defects were corrected on treated Alpl–/–?mice by this treatment. Additionally the long bone growth rates (LGR) of long bones were encouraged on treated Alpl–/–?mice compared with untreated mice. Conclusions: These results indicate that the bone-targeted TNAP treatment mediated by lentivirus can correct not only the bone disorder but also the dental symptoms in Alpl–/–. This study also shows that PLAP-D10 can potentially be used to correct HPP disease.
文摘Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutation of the gene encoding tissue non-specific alkaline phosphatase (TNSALP). Odonto-HPP is well known as the mildest of HPP. The manifestations involve only the teeth, such as premature primary teeth exfoliation caused by reduction of alveolar bone, enlarged dental pulp chamber, and dental defects. We report a case of a 9-years-old boy who developed HPP. He was observed from the primary dentition to the mixed dentition period. At initial presentation at our hospital, he had multiple premature exfoliation of primary teeth and reduction of the alveolar bone. HPP was suspected due to the low level of ALP activity in serum, his oral manifestation, and dental history. He was referred to a physician for the final diagnosis. Therefore his compound heterozygote mutations, c.1559 delT (T/delT) and c.407G > A (G/A), were found in TNSALP and he diagnosed with odonto-HPP. Even though these mutations were reported as being involved in odonto-HPP, his mineral densities tended to be lower than that of his age. It is therefore necessary to investigate the bone mineralization level in odonto-HPP without other bone symptoms. Moreover, ongoing enzyme-replacement therapy in odonto-HPP might improve dental abnormality and bone disorders.
文摘目的本研究旨在分析中国低磷酸酶血症患者的基因突变特点和常见就诊原因,提醒相关医生加以注意,以提高诊断效率。方法通过中国知网、维普中文科技期刊数据库、万方数据库、Pub Med、Ovid、Web of Science和Embase,检索截止到2015年12月31日的可能包含低磷酸酶血症的病例的文献。根据纳入与排除标准进行筛选和评价,然后提取所纳入文献中的就诊信息,进行归纳和统计分析。结果最终筛选出25篇包含中国低磷酸酶血症患者就诊信息的文献,共包含34位患者。笔者发现ALPL基因突变主要分布在5、10号外显子,其中75.0%为错义突变。34位患者中16位(47%)因乳牙早失就诊,12位(35%)因骨骼异常就诊。结论中国HP患者ALPL基因突变在外显子上的分布不同于其他种族,乳牙早失和骨骼异常是常见就诊原因。
