Lysosomal storage disease spectrum in nonimmune hydrops fetalis: a retrospective case control study

Abstract

Objectives: Nonimmune hydrops fetalis (NIHF) accounts for 90% of hydrops fetalis cases. About 15% to 29% of unexplained NIHF cases are caused by lysosomal storage diseases (LSD). We review the spectrum of LSD and associated clinical findings in NIHF in a cohort of patients referred to our institution. Methods:We present a retrospective case-control study of cases with NIHF referred for LSD biochemical testing at a single center. Cases diagnosed with LSD were matched to controls with NIHF and negative LSD testing and analyzed according to the STROBE criteria to the extent the retrospective nature of this study allowed. patients with NIHF were diagnosed with a LSD. Eight types of LSD were diagnosed: galactosialidosis 8/28 (28.6%), sialic acid storage disease (SASD) 5/28 (17.9%), mucopolysaccharidosis VII 5/28 (17.9%), Gaucher 4/28 (14.3%), sialidosis 2/28 (7.1%), GM1 gangliosidosis 2/28 (7.1%), Niemann-Pick disease type C 1/28 (3.6%), and mucolipidosis II/III 1/28 (3.6%). Associated clinical features were hepatomegaly 16/21 (76.2%) vs 22/65 (33.8%), P < .05, splenomegaly 12/20 (60.0%) vs 14/58 (24.1%), P < .05, and hepatosplenomegaly 10/20 (50.0%) vs 13/58 (22.4%) P < .05. Conclusion:The most common LSD in NIHF were galactosialidosis, SASD, mucopolysaccharidosis VII, and Gaucher disease. LSD should be considered in unexplained NIHF cases, particularly if hepatomegaly, splenomegaly, or hepatosplenomegaly is visualized on prenatal ultrasound.

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

“…Table 1 summarizes the baseline characteristics of reported pregnancies with congenital disorders of glycosylation and nonimmune hydrops fetalis. The median maternal age, reported in only three patients was 27 years (range, [26][27][28][29][30][31][32][33][34]. Race was reported in 12 patients; 58% (7/12) were Caucasian, and 42% (5/12) were Middle Eastern.…”

“…33 In a recent case-control study on LSD in NIHF, the two most common disorders resulting in NIHF were related to the metabolism of sialic acid. 34 Terminal sialic acid is a major component of N-linked and O-linked glycoproteins and glycosphingolipids (gangliosides), which could imply a shared mechanism leading to NIHF in CDG as well. Interestingly, when considering the CDG pathophysiological classification in NIHF, 17 patients with PMM2, ALG1, ALG8, ALG9, or MGAT2 variants had CDG due to Nglycosylation defects, and only one patient with COG6 variant had CDG due to multiple glycosylation defects that include both N-glycosylation as well as O-glycosylation.…”

“…Other associated IEM with NIHF include glycogenosis type IV, peroxisomal disorders, transaldolase deficiency, cholesterol metabolism inborn errors, and citric cycle defects . In a recent case‐control study on LSD in NIHF, the two most common disorders resulting in NIHF were related to the metabolism of sialic acid . Terminal sialic acid is a major component of N‐linked and O‐linked glycoproteins and glycosphingolipids (gangliosides), which could imply a shared mechanism leading to NIHF in CDG as well.…”

Prenatal mucopolysaccharidosis VII: A novel pathogenic variant identified in GUSB gene

“…Once more frequent etiologies of NIHF are ruled out, inborn errors of metabolism (IEM) should be considered. Mucopolysaccharidosis type VII (MPS VII, MIM #253220) is among the most common lysosomal storage disease diagnosed in NIFH 7 …”

Nonimmune Hydrops Fetalis—Prenatal Diagnosis, Genetic Investigation, Outcomes and Literature Review

“…The misclassification of syndromic vs. non-syndromic disorders may serve inborn errors of metabolism (IEM). Some of these disorders—particularly lysosomal storage disorders (LSDs)—may antenatally manifest only with hydrops fetalis [ 17 ]. These disorders are distinguished from monogenic syndromes by the absence of internal organ malformations, which is why they are listed separately in the NIHF classification.…”