LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 898
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size


 
  Table of Contents    
CASE REPORT  
Year : 2020  |  Volume : 63  |  Issue : 2  |  Page : 312-314
A progressive neurological condition with acquired sea-blue histiocytosis further the diagnosis of Niemann-Pick type C1 in a 10-year-old boy


1 Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
2 Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
3 Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

Click here for correspondence address and email

Date of Web Publication18-Apr-2020
 

   Abstract 


Sea-blue histiocytes in bone marrow can be associated with a number of conditions and have indeed often been reported in Niemann-Pick diseases, mostly in Niemann-Pick type B, but also Niemann-Pick type C. Rarely, it was reported to be related to a progressive neurological condition. In this work, early bone marrow aspirations in a boy following the discovery of hepatosplenomegaly at 1 month of age and later isolated splenomegaly did not reveal abnormal cells (which is not uncommon). Numerous sea-blue histiocytes were found in a repeated exam when the child was 10-year old, at a time he had developed a progressive neurological condition with frequent falls, clumsiness, slow and slurred speech, intellectual disability, dystonic movements, and dysphagia. Acquired sea-blue histiocytes should be considered initially on the basis of clinical symptoms. Whole-exome sequencing identified two variants in the NPC1 gene, leading to the diagnosis of Niemann-Pick type C1. This case points out the presence of sea-blue histiocytes in the bone marrow and has helped to reach a diagnosis of NPC1 which was very difficult to establish even after years of study. Given the rarity of this pathology and the variety of clinical presentations, it is important to communicate the possible forms of presentation of this syndrome.

Keywords: Niemann-Pick type C1, progressive neurological condition, sea-blue histiocytosis, splenomegaly

How to cite this article:
Wang L, Sun J, Xu X, Tao L, Wu D, Zhang Y. A progressive neurological condition with acquired sea-blue histiocytosis further the diagnosis of Niemann-Pick type C1 in a 10-year-old boy. Indian J Pathol Microbiol 2020;63:312-4

How to cite this URL:
Wang L, Sun J, Xu X, Tao L, Wu D, Zhang Y. A progressive neurological condition with acquired sea-blue histiocytosis further the diagnosis of Niemann-Pick type C1 in a 10-year-old boy. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Aug 11];63:312-4. Available from: http://www.ijpmonline.org/text.asp?2020/63/2/312/282714




Sea-blue histiocytosis is a rare disorder classified as either primary or acquired, most cases are secondary to inherited lipid metabolic diseases such as Niemann-Pick disease.[1],[2] Morphological findings in bone marrow, liver, spleen, gastrointestinal tract, lungs, and sometimes brain and lymphadens can be helpful for diagnosis.[1],[2] The main clinical manifestation is hepatosplenomegaly.[1],[2],[3]


   Case Report Top


A 10-year-old boy developed hepatosplenomegaly when he was 1 month old. Splenomegaly was persistent while hepatomegaly gradually disappeared. Repeated bone marrow aspirations showed no abnormal cells and screening of inherited metabolic diseases via blood and urine samples were also normal. Within regular rehabilitation training, he still underwent a progressive neurological condition, with a history of intellectual disability for the past 7 years, clumsiness for the past 6 years, dysphagia, orofacial and oromandibular dystonic movements at the age of 5 years, slow and slurred speech at the age of 6 years, and frequent falls at the age of 8 years. Abdominal examination revealed a homogeneous enlargement of the spleen but a normal liver. Neurological examination at presentation revealed involuntary movements including vertical supranuclear gaze palsy, vertical supranuclear saccades paresis, dysarthria, dysphagia, and dystonia. No family history of splenomegaly or metabolic diseases was noted.

His blood examination showed a platelet count of 86 × 109/L, normal hemoglobin, and a white blood cell count with normal differentiation. High-density lipoprotein cholesterol (HDL-C) was 0.82 mmol/L (normal: 1.16-1.42 mmol/L). Total cholesterol, low-density lipoprotein cholesterol, liver, and renal functions, infection indexes, and coagulation profile were normal. Both physical examination and imaging studies confirmed a palpable spleen [Figure 1]a. Interestingly, cranial magnetic resonance imaging revealed only white matter demyelination [Figure 1]b. Meanwhile, bone marrow aspirate and Wright-Giemsa's staining revealed the presence of hundreds of sea-blue histiocytes in the whole slide (1.5 × 3.0 cm), and large cell body of sea-blue histiocytes with eccentric and small nuclei being round or oval, and numerous plasma within different size sea-blue particles, and a network of chromatin with an occasional nucleolus [Figure 1]c. Whole-exome sequencing (WES) identified variants of c. 1211 G > A (p.R404Q) mutation from his father and c. 2054 T > C (p.I685T) mutation from his mother in NPC1.
Figure 1:CT (a) displayed splenomegaly. T2-weighted MRI (b) showed the bilaterally increased signal intensity of white matter at the lateral ventricle angle. Bone marrow aspirate (c) showed typical sea-blue histiocytes with large cell bodies, small round or oval nuclei, and different size sea-blue particles. (Wright-Giemsa's staining. ×1000)

Click here to view



   Discussion Top


The decline in HDL-C indicates that disorders of lipid metabolism should be highly suspected, in addition to a possible diagnosis of hepatolenticular degeneration, demyelinating disease, mitochondrial encephalomyopathy, and central nervous system disease.[1],[2],[3],[4] In our patient, the presence of sea-blue histiocytes in the bone marrow and thrombocytopenia led to a definite diagnosis of sea-blue histiocytes.[1],[2] Acquired sea-blue histiocytes should be considered initially on the basis of clinical symptoms.[1],[2],[3]

Sea-blue histiocytes in bone marrow can be associated with a number of conditions, and has indeed often been reported in Niemann-Pick diseases, mostly Niemann-Pick type B,[1],[2] but also Niemann-Pick type C.[3] The present study is a brief report of a clinical rather a typical case of Niemann-Pick disease type C. Early bone marrow aspirations following the discovery of hepatosplenomegaly at 1 month of age and later isolated splenomegaly did not reveal abnormal cells (which is not uncommon). Numerous sea-blue histiocytes were found in a repeated exam when the child was 10-year old, at a time he had developed a progressive neurological condition with frequent falls, clumsiness, slow and slurred speech, intellectual disability, dystonic movements, and dysphagia. WES identified two variants in the NPC1 gene, leading to the diagnosis of Niemann-Pick type C.

Niemann-Pick types A and B are due to mutations of the SMPD1 gene, encoding acid sphingomyelinase.[2],[5] Niemann-Pick type C is due to mutations of either the NPC1 or the NPC2 genes, encoding proteins involved in intracellular trafficking and lysosomal egress of cholesterol.[4],[5],[6] Both mutations have already been reported, as p.R404Q in several cases of the literature by Sun et al. (2001),[6] Meiner et al. (2001),[7] Imrie et al. (2015),[8] and as p.I685T in a Chinese case by Zhang et al. (2014).[9] Thus, this rare sea-blue histiocytes is a macrophage with lysosomal lipid accumulations secondary to NPC1.[1-4,6]


   Conclusion Top


This case points out that the presence of sea-blue histiocytes in the bone marrow and has helped to reach a diagnosis of NPC1 which was very difficult to establish after years of study. Thus, given the rarity of this pathology and the variety of clinical presentations, it is important to further communicate the possible forms of presentation of this syndrome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Suzuki O, Abe M. Secondary sea-blue histiocytosis derived from Niemann-Pick disease. J Clin Exp Hematop 2007;47:19-21.  Back to cited text no. 1
    
2.
Bermejo N, Prieto J, Arcos MJ. Sea-blue histiocytosis in bone marrow of a patient with chronic thrombocytopenia. Acta Haematol 2015;133:277-8.  Back to cited text no. 2
    
3.
Wenger DA, Barth G, Githens JH. Nine cases of sphingomyelin lipidosis, a new variant in Spanish-American Children. Juvenile variant of Niemann-Pick disease with foamy and sea-blue histiocytes. Am J Dis Child 1977;131:955-61.  Back to cited text no. 3
    
4.
Garver WS, Jelinek D, Meaney FJ, FIynn J, Pettit KM, Shepherd G, et al. The National Niemann-Pick type C1 disease database: Correlation of lipid profiles, mutations, and biochemical phenotypes. J Lipid Res 2010;51:406-15.  Back to cited text no. 4
    
5.
Vanier MT. Niemann-Pick diseases. Handb Clin Neurol 2013;113:1717-21.  Back to cited text no. 5
    
6.
Sun X, Marks DL, Park WD, Wheatley CL, Puri V, O'Brien JF, et al. Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1. Am J Hum Genet 2001;68:1361-72.  Back to cited text no. 6
    
7.
Meiner V, Shpitzen S, Mandel H, Klar A, Ben-Neriah Z, Zlotogora J, et al. Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C. Genet Med 2001;3:343-8.  Back to cited text no. 7
    
8.
Imrie J, Heptinstall L, Knight S, Strong K. Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: A 5-year update from the UK clinical database. BMC Neurol 2015;15:257.  Back to cited text no. 8
    
9.
Zhang H, Wang Y, Lin N, Yang R, Qiu W, Han L, et al. Diagnosis of Niemann-Pick disease type C with 7-ketocholesterol screening followed by NPC1/NPC2 gene mutation confirmation in Chinese patients. Orphanet J Rare Dis 2014;9:82.  Back to cited text no. 9
    

Top
Correspondence Address:
De Wu
Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, High-Tech Branch of the 1st Affiliated Hospital of Anhui Medical University, NO. 120, Wanshui Road, Hefei 230022, Anhui
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_728_19

Rights and Permissions


    Figures

  [Figure 1]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Case Report
   Discussion
   Conclusion
    References
    Article Figures

 Article Access Statistics
    Viewed367    
    Printed7    
    Emailed0    
    PDF Downloaded8    
    Comments [Add]    

Recommend this journal