Sialidosis Presenting as Severe Nonimmune Fetal Hydrops is Associated with Two Novel Mutations in Lysosomal α-Neuraminidase

Abstract

Sialidosis is a lysosomal storage disease characterized by accumulation of sialylated oligosaccharides in tissues, blood and urine and is caused by mutations in the gene for lysosomal a-neuraminidase (NEU1). There is wide variability in the age of onset and severity of symptoms in sialidosis. We report here a case of sialidosis due to novel mutations in NEU1 presenting as severe nonimmune hydrops fetalis.

Hydrops fetalis – has there been a change in diagnostic spectrum and mortality?

“…Metabolic causes should be considered, including lysosomal storage disease, which is found in 1-2% of all NIH cases [24][25][26][27][28][29][30][31]. The diagnosis can often be confirmed by assessing cultured cells (skin fibroblasts, amniotic fluid cells, or chorionic villus tissue) for specific metabolic parameters.…”

“…Six of the 40 infants who did not survive died in the delivery room (9%). Risk factors for increased mortality by univariate analysis were as follows: (1) gestational age (median 30 (28)(29)(30)(31)(32) weeks vs. 34 (31-36) weeks), (2) Apgar at 1 min (median 2 (1-4) vs. 4 (2-6)), (3) Apgar at 5 min (median 5 (1-6) vs. 6 (4-8)), (4) Apgar at 10 min (median 6 (2-7) vs.7 (6-8)), and heart failure (22 patients vs. 8 patients). Finally, the multivariate logistic regression showed gestational age as an independent variable which, combined with Apgar at 1 min, 5 min and 10 min and heart failure, allows for an 82% prediction of mortality.…”

Pathogenesis, emerging therapeutic targets and treatment in sialidosis

“…All patients with type II disease have, among other symptoms, coarse face, enlargement of spleen and liver, dysostosis multiplex, vertebral deformities, and severe mental retardation. Both the infantile patients with longer survival and the juvenile cases develop macular cherry-red spots and myoclonus, and may also have hearing loss and angiokeratoma 6, 13–15 . Their life expectancy can vary greatly depending on the associated mutations and the severity of the symptoms.…”

NEU1 Mutation in a Korean Infant with Type 2 Sialidosis Presenting as Isolated Fetal Ascites

“…3,4 A coarse face, multiple organomegaly, and a vacuolated cytoplasm in a peripheral blood smear and placental biopsy can lead to suspicion of intracellular storage disease. 1,5 Urine thin-layer chromatography for oligosaccharides, skin fibroblast NEU1 activity, and an enzymatic study of specific LSDs can help diagnosis. A high index of suspicion is the most important factor for diagnosing LSD, and if the symptoms suggest a specific diagnosis, a genetic test is helpful.…”