Fetal/Perinatal Lethal Gaucher Disease: A Case Series

Gaucher disease is a rare lysosomal storage disease caused by mutations in the GBA gene, resulting in the accumulation of glucosylceramides in macrophages. The perinatal/lethal form, also including fetal Gaucher disease, is a distinct and severe variant, usually presenting with non-immune hydrops fetalis, hepatosplenomegaly, ichthyosiform changes, and typical “Gaucher cells” seen on histology in various organs. Four cases of fetal/perinatal Gaucher disease are presented, 1 genetically confirmed and 3 histologically diagnosed, with a description of the prenatal findings and the pathological features at autopsy. In all 4 cases, hydrops was detected prenatally after the 24th week of gestation, leading to termination of pregnancy. Hepatosplenomegaly was confirmed at autopsy in 3 cases. Dysmorphic features included thick lips and eclabium, upturned nose, thick antitragus, and micropenis in the 2 male fetuses. Histologically, characteristic Gaucher cells were found in multiple organs, while in 2 cases brain involvement was reported. In conclusion, fetal Gaucher disease shows distinct pathological characteristics. Some facial features and micropenis are highlighted for the first time, whereas ichthyosiform body skin changes described in neonates and infants are not typically seen in the fetus. Brain involvement is variable. Further reporting of genotype-phenotype correlations is necessary in cases of fetal/perinatal Gaucher disease.