Prenatal hydrops fetalis associated with infantile free sialic acid storage disease due to a novel homozygous deletion in the SLC17A5 gene

Abstract

Nonimmune hydrops fetalis, the excessive accumulation of serous fluid in the subcutaneous tissues and serous cavities of the fetus, has many possible etiologies, providing a diagnostic challenge for the physician. Lysosomal storage diseases have been reported in up to 5%–16% of nonimmune hydrops fetalis pregnancies. Infantile free sialic acid storage disease (ISSD) (OMIM #269920) is a severe form of autosomal recessive sialic acid storage disease. ISSD is caused by mutations in SLC17A5 (OMIM #604322), which encodes sialin, a lysosomal-membrane sialic acid transporter. We describe a case of fetal hydrops due to a novel homozygous deletion in the SLC17A5 gene. Prenatal single-nucleotide polymorphism (SNP) array analysis was performed on amniocytes after the discovery of fetal hydrops at 24 wk gestation revealing no copy-number variants. The SNP array, however, reported several regions of homozygosity (ROHs) including one on Chromosome 6 encompassing the SLC17A5 gene. High levels of urine sialic acid in the newborn were detected. SLC17A5 gene sequencing was initiated with no sequence variants identified; however, the assay failed to amplify exons 8 and 9, prompting an exon-level copy-number analysis that revealed a novel homozygous deletion of exons 8 and 9, inherited from heterozygous carrier parents. ISSD should be considered in the workup of patients with nonimmune hydrops fetalis, and analysis for SLC17A5 deletions should be carried out when variants are not detected by gene sequencing.

Detection of Structural Variants by NGS: Revealing Missing Alleles in Lysosomal Storage Diseases

“…Similarly, a partial MCOLN1 gene deletion (c.1_788del) has been detected and described in patients with Mucolipidosis Type IV and identified as founder mutation in the Ashkenazi Jewish population [ 104 ], while a homozygous 94 bp deletion and a homozygous deletion of exons 8–9 in SLC17A5 were found in a child and in a prenatal hydrops fetalis with infantile free sialic acid storage disease, respectively [ 105 , 106 ].…”