Case Report: From suspected congenital rubella to a lysosomal storage disorder-diagnostic challenges in a neonate with findings strongly suggestive of Gaucher disease.

BACKGROUND: Neonatal lysosomal storage disorders may overlap clinically with congenital infection. We report a term infant initially evaluated for congenital rubella because of petechiae, thrombocytopenia, hepatosplenomegaly, cholestasis, bilateral non-pass results on newborn hearing screening, cardiac abnormalities, and ocular findings.

CASE PRESENTATION: A term male neonate presented with petechiae, gastrointestinal bleeding, thrombocytopenia, hepatosplenomegaly, cholestasis, liver dysfunction, bilateral non-pass newborn hearing-screening results, cardiac abnormalities, and ocular findings after repeated maternal rubella immunoglobulin M and G positivity during pregnancy. Infant rubella immunoglobulin G was positive and immunoglobulin M was negative, but rubella-specific reverse-transcription polymerase chain reaction and adequate longitudinal serology were not performed. Dried-blood-spot (DBS) glucocerebrosidase activity was 0.96 μmol/L/h (reference interval, 1.19-22.23), only modestly reduced, whereas glucosylsphingosine (lyso-Gb1) was 963.66 ng/mL (reference value, <17.41), more than 55-fold the upper limit. Neither result was confirmed in an independently collected specimen, and no leukocyte or fibroblast enzyme assay was performed. Long-range polymerase chain reaction and sequencing reported GBA1 c.1265_1319del as apparently homozygous, but parental Sanger testing detected the variant in the father and not the mother. Biallelic GBA1 involvement therefore remained unresolved. Alternative neonatal lysosomal disorders were not systematically excluded. The findings were consistent with probable neonatal-onset Gaucher disease but did not establish a definitive diagnosis. The infant was discharged after 21 days and was reported to have died at 6 months; the intervening course and certified cause of death were unavailable.

CONCLUSION: This case illustrates diagnostic uncertainty in neonates with overlapping infectious, haematological, inflammatory, and lysosomal features. Markedly elevated lyso-Gb1 provided the strongest Gaucher-directed biochemical evidence, whereas the modestly reduced single dried-blood-spot enzyme result and unresolved GBA1 segregation precluded definitive confirmation. Relevant Gaucher-like and hepatosplenic lysosomal disorders were not systematically excluded. The findings were consistent with probable neonatal-onset Gaucher disease; congenital rubella remained unconfirmed and could not be fully excluded, and the disease subtype, allelic configuration, inheritance mechanism, and recurrence risk remained undetermined.