비면역 태아수종을 보인 infantile sialic acid storage disease 환자의 생화학적 분자유전학적 특징
Biochemical and molecular analyses of infantile sialic acid storage disease in a patient with nonimmune hydrops fetalis
Abstract
Nonimmune hydrops fetalis (NIH) is the most severe clinical manifestation of lysosomal storage diseases (LSDs). Around 14 different LSDs have been accounted for as 1-15% of the cause of nonimmune hydrops fetalis. We report a Korean infant affected by an extremely rare but severe form of infantile sialic acid storage disease (ISSD). The first offspring of non-consanguineous Korean parents presented with NIH at 22 weeks of gestation. The patient was born at 33 weeks and 6 days of gestation with a birth weight of 2170 g and was requiring high frequency oscillatory ventilation soon after birth. She was hypotonic and had coarse facial features, generalized edema with ichthyosis and telangiectasias, and hepatosplenomegaly. LSD was suspected based on the dysostosis multiplex in simple X-ray and the presence of diffuse vacuolation of syncytiotrophoblast, villous stromal cells, and intermediated trophoblast in placental biopsy. The urinary excretions of total sialic acid and free sialic acid measured by liquid chromatography-tandem spectrometry were 392.16 mmol/mol creatinine (normal control, 55.11 ± 0.83) and 199.03 mmol/mol creatinine (normal control, 19.41 ± 5.30), respectively. The patient was compound heterozygous of the c.908G>A (p.Trp303Ter) and the splicing mutation c.1529+5G>A (IVS9+5 G>T) in the SLC17A5 gene. ISSD could be underdiagnosed, because diagnosis is based on clinical suspicion and urinary sialic acid testing is less widely available. Our ISSD patient was manifested with NIH, dysmorphic face, hepatosplenomegaly, dysostosis multiplex, and histologic findings of placenta indicating LSDs. Definite diagnosis of ISSD is made on the basis of elevated urinary free sialic acid excretion and molecular studies. This underscores that ISSD should be considered and included in the differential diagnosis of NIH.