A Neonatal Case With Perinatal Lethal Gaucher Disease Associated With Missense G234E and H413P Heterozygous Mutations

Abstract

Perinatal lethal Gaucher disease (PLGD), a particular and serious form of type 2 Gaucher disease (GD), often causes lethality in utero or death within hours after birth. The typical clinical manifestations include non-immune hydrops fetalis (NIHF), premature birth, fetal growth restriction, fetal intrauterine death, or neonatal distress and rapid death after birth. Here, we present a premature neonate with GD whose main clinical manifestations included intrauterine growth retardation, anasarca, facial dysmorphia, ichthyosis, respiratory distress, hepatosplenomegaly, joint contractures, myoclonus, refractory thrombocytopenia, anemia, elevated levels of liver enzymes, bile acid and direct bilirubin, cholestasis, pulmonary hypoplasia, intracranial hemorrhage, and abnormal electroencephalogram. The activity of β- glucocerebrosidase was 0 in the peripheral white blood cells of the neonate. The sequencing analysis identified the presence of missense G234E and H413P heterozygous mutations in glucerebrosidase (GBA) exon 7 and 10, with the latter first observed to be associated with PLGD. This infant died at 73 days of age.

Keywords: convulsions; hepatosplenomegaly; ichthyosis; premature neonate; thrombocytopenia.

Figure 1

Prenatal onsets (A) oligohydramnios; (B) The normal heart silhouette, increased cardiothoracic ratio and small lung volume demonstrating pulmonary hypoplasia.

Figure 2

Clinical phenotype: facial dysmorphia; pinna development deformity; ichthyosis, joint contractures, anasarca; peeling skin on limbs and groin. The black line shows the boundaries of the liver and spleen, indicating hepatosplenomegaly; small microcaulia.

Figure 3

(A) Lack of air in the lung; (B) Multiple hemorrhagic lesions in the left frontal, temporal and parietal lobes.

Figure 4

Genotyping results: (A) Chromatograms showing DNA sequencing results for the proband and parents. Genomic DNA isolated from leukocytes (proband, mother, and father) demonstrated a novel heterozygous A-to-C transition at position 1,238 in exon 10 of the GBA gene was identified in the proband, which resulted in a His413Pro mutation. The mutation was not detected in the parental genomic DNA. (B) A heterozygous G-to-A transition at position 701 in exon 7 of the GBA gene in the mother and the proband, which resulted in a Gly234Glu mutation in the maternal and proband's genomic DNA.