Matsushita Masaki, Mishima Kenichi, Nagata Tadashi, Kamiya Yasunari, Imagama Shiro, Kitoh Hiroshi
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Orthopaedic Surgery, Aichi Children's Health and Medical Center, Aichi, Japan.
Clin Pediatr Endocrinol. 2021;30(1):53-56. doi: 10.1297/cpe.30.53. Epub 2021 Jan 5.
Hypophosphatasia (HPP) is a rare skeletal dysplasia characterized by impaired bone mineralization, caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase () gene. Enzyme replacement therapy (ERT) by administration of asfotase alfa was reported to improve the survival rate, bone mineralization, and short stature in the severe form of HPP. However, the effect of asfotase alfa in improving the skeletal phenotypes for the mild form of HPP has not been elucidated. We report a case with perinatal benign HPP who had compound heterozygous mutations of p.F327L and p.R30X in the gene. No hypomineralization was seen in the radiographs from the neonatal period, but bowing of the femurs and ulnares bilaterally was persistent. ERT was administered during the age of 7.8 to 10.8 yr, although there was an interruption in the treatment for one year. The bowed femurs and ulnares were not improved by the treatment with asfotase alfa at the age of 10.8 yr. Bone mineral density of the lumbar spine was between -0.5 and -1.0 of the z-score, and the patient's height was about -2.0 SD during the treatment. Asfotase alfa might have a limited effect in improving the bowed limbs in perinatal benign hypophosphatasia.
低磷性佝偻病（HPP）是一种罕见的骨骼发育不良疾病，其特征为骨矿化受损，由组织非特异性碱性磷酸酶（TNAP）基因的功能丧失性突变引起。据报道，通过给予阿法骨化醇进行酶替代疗法（ERT）可提高重症HPP患者的生存率、改善骨矿化并缓解身材矮小症状。然而，阿法骨化醇对轻症HPP骨骼表型的改善作用尚未阐明。我们报告了一例围产期良性HPP病例，该患者的TNAP基因存在p.F327L和p.R30X复合杂合突变。新生儿期X线片未见矿化不足，但双侧股骨和尺骨弯曲持续存在。患者在7.8至10.8岁期间接受ERT治疗，尽管治疗中断了一年。在10.8岁时，阿法骨化醇治疗并未改善弯曲的股骨和尺骨。治疗期间，腰椎骨密度的z值在-0.5至-1.0之间，患者身高约低于标准差2.0。阿法骨化醇对改善围产期良性低磷性佝偻病的肢体弯曲可能效果有限。
