B형 Niemann-Pick 병에 이환된 한국인 성인 1예: 이차성 Sea-blue 조직구증 및 분자적 특성 규명 = Case of a Korean Adult Affected by Type B Niemann-Pick Disease: Secondary Sea-blue Histiocytosis and Molecular Characterization

다국어 초록 (Multilingual 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.

국문 초록 (Abstract)

Niemann-Pick 병(Niemann-Pick disease, NPD)은 SMPD1
유전자에 의해 생성되는 효소인 산성스핑고마이엘린분해효소가
결핍되는 유전성 대사질환이다. 유아기의 심한 신경변성질환으
로 발현하는 A형 NPD와는 달리 B형 NPD 환자들은 신경변성이
없거나 경미하므로 성인기까지 생존하는 경우가 많다. 현재까지
100개가 넘는 SMPD1 돌연변이가 NPD를 유발하는 것으로 알
려져 있는데, 한국인 NPD 환자의 SMPD1 돌연변이에 대한 보
고는 1예에 불과하다. 증례는 32세 여자 환자로 신경학적 증상
없이 혈소판감소증을 주소로 내원하였다. 이학적 검진과 방사선
학적 검사에서 간비종대가 있었고, 흉부방사선검사에서는 간질
성폐질환에 합당한 소견이 관찰되었다. 생화학 검사에서는 간효
소, 총 콜레스테롤, 중성지방, LDL-콜레스테롤 증가, HDL-콜
레스테롤 감소 등을 보였고, 골수 및 간생검에서 sea-blue 조직
구 또는 공포성 포말조직구가 관찰되었다. 말초혈액 백혈구에서
추출한 genomic DNA를 이용한 SMPD1 유전자의 염기서열분
석 결과 엑손 2에서 p.E246K와 p.A357V 돌연변이가 복합이형
접합자로 확인되었다. 전자는 이탈리아 환자에서 보고된 바 있
으나, 후자는 아직 보고된 바가 없다. 환자는 고지혈증 치료를
위해 rosuvastatin을 1일 10 mg의 용량으로 4개월간 복용하였
다. 본 증례는 한국인 NPD 환자에서 SMPD1 유전자의 돌연변
이가 확인된 2번째 예이다. 앞으로는 B형 NPD의 특징적인 소
견을 보이는 환자들에서 적극적인 SMPD1 유전자 분석을 실시
해 B형 NPD의 진단을 촉진하고 한국인 NPD 환자군의 분자적
특성에 대한 자료를 축적해야 할 것이다.

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