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Chronic thrombocytopenia and skeletal dysplasia in a 14-year-old girl with cystic fibrosis

Jan C. Thomassen

Cystic Fibrosis Center Cologne, University Children´s Hospital Cologne, Faculty of Medicine, University of Cologne, Germany

E-mail : aa

Ilse J. Broekaert

Cystic Fibrosis Center Cologne, University Children´s Hospital Cologne, Faculty of Medicine, University of Cologne, Germany

Friederike Körber

Department of Pediatric Radiology, University Children´s Hospital Cologne, Germany

Thorsten Simon

Pediatric Hematology and Oncology, University Children´s Hospital Cologne, Germany

Ernst Rietsche

Cystic Fibrosis Center Cologne, University Children´s Hospital Cologne, Faculty of Medicine, University of Cologne, Germany

Silke van Koningsbruggen-Rietsche

Cystic Fibrosis Center Cologne, University Children´s Hospital Cologne, Faculty of Medicine, University of Cologne, Germany

DOI: 10.15761/CCRR.1000282.

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Key words

 cystic fibrosis, chronic thrombocytopenia, skeletal dysplasia, Shwachman-Bodian-Diamond syndrome

Abbreviations

 CF: Cystic Fibrosis; SBDS: Shwachman-Bodian-Diamond Syndrome; PI: Pancreas Insufficiency; NOF: Non-Ossifying Fibroma

A 14-year-old Caucasian female with genetically confirmed diagnosis of cystic fibrosis (CF) (ΔF508/N1303K) and chronic exocrine pancreatic insufficiency (PI) presented with increasing pain of both knees. She developed a progressive chronic thrombocytopenia without any clinical symptoms (Table 1). Autoimmunological, rheumatological and infectiological causes were ruled out and the diagnosis of Shwachman-Bodian-Diamond Syndrome (SBDS) was established in 2009. Molecular genetic analysis detected a heterozygous missense-mutation in the SBDS-gene (c.127G>T for p.Val43Leu) of unknown clinical significance.

Table 1. Blood count over the past years (2009 diagnosis of SBDS; 2014 non-ossifying fibromas) –annual lowest values are shown.

Year

Thrombocytes (/nl)   (normal range: 150-400)

Leucocytes (x1E9/l) (normal range:4.5-17.5)

abs. Neutrophils (x1E9/l) (normal range: 1.5-9.9)

Hemoglobin (g/dl)  (normal range: 11.5-15.0)

2009

88

4.05

2.44

11.4

2010

110

4.75

2.67

11.6

2011

80

3.92

1.97

12.5

2012

81

3.86

1.64

12.2

2013

79

3.79

0.48

12.7

2014

30

4.12

1.95

11.2

2015

71

3.40

1.67

12.2

X-rays of both knees showed bilateral cystic structures of the distal femoral diametaphysis (Figure 1). Magnetic resonance imaging (Figure 2) supported the diagnosis of non-ossifying fibroma (NOF) without evidence of malignancy confirmed by histopathological results. A bone marrow biopsy was performed which excluded major complications of SBDS (myelodysplastic syndrome and acute myeloid leukemia). In consequence of the persisting pain despite analgesic treatment, curettage and spongioplasty of the bone lesions were performed. The pain resolved four weeks after surgical intervention while the asymptomatic thrombocytopenia further persisted.

Figure 1. Hyperlucent lesions of the right and left femoral diametaphysis (X-ray a.p.) with thin sclerotic rims

Figure 2. 3,8 cm x 1,2 cm measured, exentric lesion of the right and left femoral diametaphysis appearing hypointense in T1WI with peripheral low signal rims, which correspond to the sclerotic border (Coronal T1-weighted MRI-sequence).

The combination of exocrine PI, chronic thrombocytopenia and skeletal dysplasia represents the characteristic phenotype of SBDS and allows the clinical diagnosis without genetic confirmation [1,2]. The detection of mutations in the SBDS-gene may lead to an early diagnosis of SBDS before the full clinical spectrum is present. However, mutations in an homozygous status can only be found in approximately 90% of SBDS-patients [1,3].

This case demonstrates the difficulties in establishing the diagnosis of SBDS especially in patients with other chronic diseases sharing similar symptoms (e.g. PI which was contributed solely to CF after birth). PI in SBDS can improve within the first years of life whereas in CF the PI is irreversible due to fibrotic changes in the organ.

Quarterly blood counts during the routine CF-visits were scheduled and with regard to haematological complications, annual bone marrow biopsies were recommended [1].  

References

  1. Dror Y, Donadieu J, Koglmeier J, Dodge J, Toiviainen-Salo S, et al. (2011) Draft Consensus guidelines for diagnosis and  treatment of Shwachman-Diamond Syndrome. Ann N Y Acad Sci 1242: 40-55. [Crossref]
  2. Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, et al. (2014) Variable clinical presentation of SDS: update from the North American SDS Registry. J Pediatr 164: 866-70. [Crossref]
  3. Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, et al. (2003) Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet 33: 97-101. [Crossref]

Editorial Information

Editor-in-Chief

Andy Goren
University of Rome "G.Marconi"

Article Type

Case Report

Publication history

Received date: October 20, 2016
Accepted date: November 11, 2016
Published date: November 15, 2016

Copyright

©2016 Thomassen JC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Thomassen JC, Broekaert IJ, Körber F, Simon T, Rietschel E, et al. (2016) Chronic thrombocytopenia and skeletal dysplasia in a 14-year-old girl with cystic fibrosis. Clin Case Rep Rev 2: doi: 10.15761/CCRR.1000282.

Corresponding author

Jan Christoph Thomassen

CF Study Center Cologne, University Hospital Cologne Kerpenerstr. 62, 50924 Cologne, Germany, Tel: +49-221-478-4492; Fax: +49-221-478-3330.

Table 1. Blood count over the past years (2009 diagnosis of SBDS; 2014 non-ossifying fibromas) –annual lowest values are shown.

Year

Thrombocytes (/nl)   (normal range: 150-400)

Leucocytes (x1E9/l) (normal range:4.5-17.5)

abs. Neutrophils (x1E9/l) (normal range: 1.5-9.9)

Hemoglobin (g/dl)  (normal range: 11.5-15.0)

2009

88

4.05

2.44

11.4

2010

110

4.75

2.67

11.6

2011

80

3.92

1.97

12.5

2012

81

3.86

1.64

12.2

2013

79

3.79

0.48

12.7

2014

30

4.12

1.95

11.2

2015

71

3.40

1.67

12.2

Figure 1. Hyperlucent lesions of the right and left femoral diametaphysis (X-ray a.p.) with thin sclerotic rims

Figure 2. 3,8 cm x 1,2 cm measured, exentric lesion of the right and left femoral diametaphysis appearing hypointense in T1WI with peripheral low signal rims, which correspond to the sclerotic border (Coronal T1-weighted MRI-sequence).