Nakamura-Utsunomiya Akari, Okada Satoshi, Hara Keiichi, Miyagawa Shinichiro, Takeda Kanae, Fukuhara Rie, Nakata Yusei, Hayashidani Michiko, Tachikawa Kanako, Michigami Toshimi, Ozono Keiichi, Kobayashi Masao
Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Clin Pediatr Endocrinol. 2010 Jan;19(1):7-13. doi: 10.1297/cpe.19.7. Epub 2010 Mar 11.
Hypophosphatasia is a rare inherited disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. It is classified into 6 subtypes, and the perinatal lethal form of hypophosphatasia is the most severe. Patients with this form suffer from various symptoms, including respiratory failure, premature craniosynostosis, rachitic changes in the metaphyses, convulsions and hypercalcemia. This report presents 6 cases of the perinatal lethal form of hypophosphatasia. All of the patients showed shortening of the long bones in utero in ultrasonographic examinations. Two of the six patients died at birth because they could not establish spontaneous breathing. Three of the remaining four patients also died before 1 yr of age. The major cause of death was respiratory failure due to hypoplastic lung. All of the patients, except for the two who died at birth, experienced convulsions in their clinical courses. Vitamin B6 therapy effectively reduced the frequency and severity of convulsions. However, it could not always make the patients convulsion free. Three patients underwent a genetic analysis. The 1559delT mutation, which abolishes Alkaline Phosphatase (ALP) activity, was a hot spot. A homozygous 1559delT mutation was observed in two patients. However, they differed in severity of symptoms. Although a good genotype-phenotype correlation has been reported in hypophosphatasia, the genotype alone does not always predict the life span of the patients. These cases therefore suggested the importance of genetic counseling.
低磷酸酯酶症是一种由组织非特异性碱性磷酸酶活性缺乏引起的罕见遗传性疾病。它分为6种亚型，其中围产期致死型低磷酸酯酶症最为严重。患有这种类型的患者会出现各种症状，包括呼吸衰竭、颅骨过早融合、干骺端佝偻病样改变、惊厥和高钙血症。本报告介绍了6例围产期致死型低磷酸酯酶症病例。所有患者在超声检查中均显示宫内长骨缩短。6例患者中有2例出生时死亡，因为他们无法自主呼吸。其余4例患者中有3例也在1岁前死亡。主要死亡原因是肺发育不全导致的呼吸衰竭。除2例出生时死亡的患者外，所有患者在临床过程中均出现惊厥。维生素B6治疗有效降低了惊厥的频率和严重程度。然而，它并不能总是使患者不再惊厥。3例患者进行了基因分析。消除碱性磷酸酶（ALP）活性的1559delT突变是一个热点。在2例患者中观察到纯合的1559delT突变。然而，他们的症状严重程度不同。尽管低磷酸酯酶症中已报道有良好的基因型-表型相关性，但仅基因型并不总是能预测患者的寿命。因此，这些病例表明了遗传咨询的重要性。
