Korean J Lab Med.  2009 Apr;29(2):97-103. 10.3343/kjlm.2009.29.2.97.

A Case of a Korean Adult Affected by Type B Niemann-Pick Disease: Secondary Sea-blue Histiocytosis and Molecular Characterization

• Cho YU
• Chae JD
• Lee WM
• Woo JJ
• Lee HB
• Gong SJ
• Park CJ
• Kim GH
• Yoo HW

• KMID: 854963
• DOI: http://doi.org/10.3343/kjlm.2009.29.2.97

Abstract

Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.

Keyword

Type B Niemann-Pick disease; SMPD1 mutation; Sea-blue histiocytes

MeSH Terms

Adult
Base Sequence
Bone Marrow Cells/pathology
Female
Humans
Korea
Liver/pathology
Niemann-Pick Disease, Type B/*diagnosis/genetics/radiotherapy
Pregnancy
Sea-Blue Histiocyte Syndrome/diagnosis/pathology
Sequence Analysis, DNA
Sphingomyelin Phosphodiesterase/genetics
Tomography, X-Ray Computed

Figure

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  Fig. 1. Images of chest PA and high resolution CT. (A) Chest radiograph shows subtle widespread reticulonodular pattern with peripheral septal thickening. (B) High resolution CT image through both upper lobes demonstrates diffuse thickening of the interlobular septa and intralobular interstitium.

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  Fig. 2. Pictures of bone marrow aspirate smear and biopsy section. (A) Bone marrow aspirate smear illustrates a typical sea-blue histiocyte with voluminous cytoplasm containing numerous coarse, basophilic granules (arrowhead), a finely vacuolated foamy Niemann-Pick cell (arrow), and an intermediate form (double arrow) (Wright stain, ×1,000). (B) The histiocytic infiltrates exhibit a patchy, clustered appearance on the bone marrow biopsy section (H&E stain, ×400).

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  Fig. 3. Pictures of liver biopsy. (A) The hepatocytes are diffusely swollen and have pale and bubbly cytoplasm, and are admixed with foamy histiocytes (H&E stain, ×400). (B) CD68 immunostaining reveals abundant foamy histiocytes between hepatocytes (Immunohistochemical stain, ×400).

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  Fig. 4. Results of SMPD1 gene sequencing analysis. The upper electropherogram shows heterozygous c.736G>A (p.E246K), and the lower one does heterozygous c.1070C>T (p.A357V). Arrows mark the location of each mutation. Nucleotide numbers are derived from cDNA SMPD1 sequences (RefSeq NM_001007593.1).

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