Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
J Med Case Rep. 2021 Nov 26;15(1):573. doi: 10.1186/s13256-021-03167-9.
In neonates, rhesus D alloimmunization despite anti-D immunoglobulin prophylaxis is rare and often unexplained. Rhesus D alloimmunization can lead to hemolytic disease of the newborn with anemia and unconjugated hyperbilirubinemia. In past reports, transient congenital hyperinsulinism has been described as a rare complication of rhesus D alloimmunization. Our case report illustrates that rhesus D alloimmunization can result in a pseudosyndrome with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia, despite correctly administered anti-D immunoglobulin prophylaxis.
We report of a 36-year-old, Caucasian gravida 1, para 1 mother with A RhD negative blood type who received routine antenatal anti-D immunoglobulin prophylaxis. Her full term newborn boy presented with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia up to 295 µmol/L (ref. < 9), accounting for 64% of the total bilirubin. Syndromic congenital hyperinsulinism was suspected. Examinations showed a positive direct antiglobulin test, initially interpreted as caused by irregular antibodies; diffuse congenital hyperinsulinism by 18F-DOPA positron emission tomography/computed tomography scan; normal genetic analyses for congenital hyperinsulinism; mildly elevated liver enzymes; delayed, but present bile excretion by Tc99m-hepatobiliary iminodiacetic acid scintigraphy; and cholestasis and mild fibrosis by liver biopsy. The maternal anti-D titer was 1:16,000 day 20 postpartum. Y-chromosome material in the mother's blood could not be identified. This could, however, not exclude late intrapartum fetomaternal hemorrhage as the cause of immunization. No causative genetic findings were deetrmined by trio whole exome sequencing. The child went into clinical remission after 5.5 months.
Our case demonstrates that rhesus D alloimmunization may present as a pseudosyndrome with transient congenital hyperinsulinism, anemia, and inspissated bile syndrome with conjugated hyperbilirubinaemia, despite anti-D immunoglobulin prophylaxis, possibly due to late fetomaternal hemorrhage.
在新生儿中，尽管进行了抗-D 免疫球蛋白预防，RhD 同种免疫仍很少见且常无法解释。RhD 同种免疫可导致新生儿溶血病，伴有贫血和未结合高胆红素血症。在过去的报告中，短暂性先天性胰岛素瘤被描述为 RhD 同种免疫的罕见并发症。我们的病例报告表明，尽管进行了正确的抗-D 免疫球蛋白预防，但 RhD 同种免疫仍可导致严重的先天性胰岛素瘤、贫血和结合高胆红素血症的假性综合征。
我们报告了一位 36 岁的白人初产妇，1 次妊娠，1 次分娩，血型为 RhD 阴性，接受了常规的产前抗-D 免疫球蛋白预防。她的足月男婴出生时患有严重的先天性胰岛素瘤、贫血和结合高胆红素血症，胆红素值高达 295µmol/L（参考值<9），占总胆红素的 64%。怀疑为综合征性先天性胰岛素瘤。检查显示直接抗球蛋白试验阳性，最初解释为不规则抗体引起；18F-DOPA 正电子发射断层扫描/计算机断层扫描显示弥漫性先天性胰岛素瘤；先天性胰岛素瘤的基因分析正常；肝酶轻度升高；Tc99m-肝胆汁酸放射性核素扫描显示胆汁排泄延迟但存在；肝活检显示胆汁淤积和轻度纤维化。母亲产后 20 天的抗-D 效价为 1:16,000。母亲血液中的 Y 染色体物质无法识别。然而，这不能排除分娩期间晚期胎儿-母亲出血是免疫的原因。通过 trio 全外显子组测序未确定致病基因。患儿在 5.5 个月后临床缓解。
我们的病例表明，尽管进行了抗-D 免疫球蛋白预防，RhD 同种免疫仍可能表现为假性综合征，伴有短暂性先天性胰岛素瘤、贫血和浓稠胆汁综合征伴结合高胆红素血症，可能是由于晚期胎儿-母亲出血。
