Fukushima Kazunori, Kawai-Kowase Keiko, Yonemoto Yukio, Fujiwara Makoto, Sato Hiroko, Sato Mahito, Kubota Takuo, Ozono Keiichi, Tamura Junich
Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Department of General Medicine, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
J Med Case Rep. 2019 Apr 24;13(1):101. doi: 10.1186/s13256-019-2045-4.
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.
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.
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.
低磷酸酯酶症是一种遗传性骨病，其特征是由ALPL编码的碱性磷酸酶活性降低。临床上，根据首次出现症状或牙齿表现的年龄，低磷酸酯酶症可分为围生期、婴儿期、儿童期和成人型，以及牙型低磷酸酯酶症。成人低磷酸酯酶症通常出现在中年患者中，这些患者在成年早期看似健康，表现为下肢反复出现的、愈合缓慢的应力性骨折导致的足部疼痛。由于成人低磷酸酯酶症的症状多样且常见，许多低磷酸酯酶症患者可能未被准确诊断，因此可能接受不恰当的治疗。
我们报告一例35岁日本女性病例，其在常规体检时发现血清碱性磷酸酶水平低。她有轻度肌肉/骨骼疼痛，但无佝偻病、骨折或牙齿问题病史。腰椎和股骨颈骨密度测量显示骨量减少，低于年轻成年人的预期范围。腹部超声检查发现双肾有大量微钙化。尿液氨基酸分析显示磷酸乙醇胺升高。血清碱性磷酸酶活性低、磷酸乙醇胺升高和骨密度低支持低磷酸酯酶症的诊断。ALPL突变分析发现两个突变：p.Phe327Leu和c.1559delT。这些基因异常先前在围生期、婴儿期和儿童期低磷酸酯酶症中报道过，但在成人低磷酸酯酶症中未报道过。根据临床表现、实验室和影像学检查结果以及基因分析，该患者被明确诊断为成人低磷酸酯酶症。据我们所知，这是首例具有复合杂合突变p.Phe327Leu和c.1559delT的成人低磷酸酯酶症病例报告。
尽管该病例骨折风险高，但骨质疏松症和低磷酸酯酶症的治疗方法不同。由于成人低磷酸酯酶症症状多样，诊断往往困难，在血清碱性磷酸酶水平低的鉴别诊断中应考虑低磷酸酯酶症。早期诊断很重要，以便能开始适当治疗。
