Heo Ju Sun, Choi Ka Young, Sohn Se Hyoung, Kim Curie, Kim Yoon Joo, Shin Seung Han, Lee Jae Myung, Lee Juyoung, Sohn Jin A, Lim Byung Chan, Lee Jin A, Choi Chang Won, Kim Ee-Kyung, Kim Han-Suk, Kim Beyong Il, Choi Jung-Hwan
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
Korean J Pediatr. 2012 Nov;55(11):438-44. doi: 10.3345/kjp.2012.55.11.438. Epub 2012 Nov 23.
Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of β-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.
黏脂贮积症 II 型(ML II)或包涵体细胞病(I 细胞病)是一种罕见的常染色体隐性溶酶体酶靶向疾病。这种疾病通常发生在 6 至 12 个月大的个体中,临床表型类似于Hurler 综合征,放射学表现类似于多发性骨发育异常。然而,我们遇到了一例罕见的 ML II 型婴儿病例,该婴儿在出生前就出现了骨骼发育异常,并在出生时具有严重继发性甲状旁腺功能亢进的典型临床特征。一名女婴在妊娠 37(+1)周时出生,出生体重为 1690 g(<第 3 百分位数)。产前超声检查结果显示胎儿宫内生长受限和骨骼发育异常。出生时,该患者具有 ML II 的特征性表现,骨骼 X 光片显示多发性骨发育异常,类似于佝偻病。此外,患者碱性磷酸酶和甲状旁腺激素水平升高,符合严重的新生儿继发性甲状旁腺功能亢进。白细胞中β-D-己糖胺酶和α-N-乙酰葡糖胺酶的活性中度降低,但血浆中活性高 5 至 10 倍。胎盘活检标本检查显示滋养层细胞和合体滋养层细胞有泡沫状空泡变化。通过 GNPTAB 基因检测确诊为 ML II,结果显示存在 c.3091C>T(p.Arg1031X)和 c.3456_3459dupCAAC(p.Ile1154GlnfsX3)的复合杂合性,后者是一种新的突变。该婴儿接受了维生素 D 补充剂治疗,但在 2 个月大时因窒息死亡。