Clinical characteristics of perinatal lethal hypophosphatasia: a report of 6 cases.
Clinical characteristics of perinatal lethal hypophosphatasia: a report of 6 cases.
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DOI：
10.1297/cpe.19.7
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发表时间：
2010-01
期刊：
影响因子：
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通讯作者：
Kobayashi M
中科院分区：
文献类型：
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作者：
Nakamura-Utsunomiya A;Okada S;Hara K;Miyagawa S;Takeda K;Fukuhara R;Nakata Y;Hayashidani M;Tachikawa K;Michigami T;Ozono K;Kobayashi M
低磷症是一种罕见的遗传性疾病，由组织非特异性碱性磷酸酶活性不足引起。分为6个亚型，以围产期致死型低磷血症最为严重。这种类型的患者会出现各种症状，包括呼吸衰竭、早发的颅缝早闭、干骺端瘘管性改变、抽搐和高血钙症。本文报告6例围产期致死型低磷酸盐血症。所有患者超声检查均显示宫内长骨变短。六名患者中有两名在出生时死亡，因为他们无法建立自主呼吸。其余4名患者中有3名也在1岁之前死亡。死亡原因主要为肺发育不良所致呼吸衰竭。除了出生时死亡的两名患者外，所有患者在临床过程中都经历了抽搐。维生素B6治疗有效地降低了惊厥的频率和严重程度。然而，它并不能总是使患者的抽搐消失。三名患者接受了基因分析。取消碱性磷酸酶(ALP)活性的1559delT突变是一个热点。在两名患者中观察到1559delT纯合子突变。然而，他们在症状严重程度上有所不同。虽然在低磷酸盐血症中报道了良好的基因型-表型相关性，但单凭基因型并不总是能预测患者的寿命。因此，这些案例表明了遗传咨询的重要性。
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.