Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome

BMC Med Genomics. 2022 Sep 16;15(1):196. doi: 10.1186/s12920-022-01353-2.

PMID: 36114502

Zhe-Wen Zhou, Shou-Hao Wang, Cheng-An Xu

Highlights: This article reports a case of Niemann Pick disease type B with sea-blue histiocytes that was misdiagnosed as Budd-Chiari syndrome for three years.

Abstract

Background: Niemann Pick disease type B (NPDB), also known as the chronic visceral subtype of acid sphingomyelinase deficiency, is an uncommon autosomal recessive genetic condition brought on by mutations in the SMPD1 gene. Because it lacks unique clinical characteristics, NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS). This makes diagnosis challenging.

Case presentation: Here, a case is presented with NPDB with SBH that received a three-year BCS diagnosis in error. An imaging observation of a thin hepatic vein and fast blood flow at the junction of the hepatic vein and inferior vena cava in a 20-year-old woman with abdominal distension, hepatosplenomegaly, and hematological abnormalities led to the first diagnosis of BCS. Sea-blue histiocytes were discovered in her bone marrow by cytology. A liver biopsy revealed hepatocytes with foamy cytoplasm around by plenty of Kupffer cells. Two missense variants in the heterozygous condition were discovered after sequencing the SMPD1 gene: C.829 T > C (p.Trp277Arg) in exon 2 (novel), and c.1805 G > A (p.Arg602His) in exon 6 (already described). The diagnosis of NPDB was established by these findings.

Conclusion: Hepatosplenomegaly, hematological abnormalities, and dyslipidemia were all observed in the patient. Therefore, NPDB should be taken into account when related disorders have been excluded. Clinical signs and symptoms, common laboratory testing, and liver biopsy and gene sequencing all supported the diagnosis of NPDB. It is necessary to conduct more research on the new mutation c.829 T > C in exon 2 of the SMPD1 gene.

Keywords: Budd-Chiari syndrome, Case report, Niemann Pick disease type B, SMPD1 gene, Sea-blue histiocytosis