Subscribe to RSS
DOI: 10.1055/s-0041-1736560
Autoimmune Hemolytic Anemia Due to Spondyloenchondrodysplasia with Spastic Paraparesis and Intracranial Calcification due to Mutation in ACP5
![](https://www.thieme-connect.de/media/10.1055-s-00029027/202401/lookinside/thumbnails/10-1055-s-0041-1736560_2100019-1.jpg)
Abstract
Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5, playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the ACP5 gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.
Keywords
SPENCD - spondyloenchondrodysplasia - autoimmune hemolytic anemia - intracranial calcification - paraparesisPublication History
Received: 03 March 2021
Accepted: 16 September 2021
Article published online:
02 November 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Briggs TA, Rice GI, Daly S. et al. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet 2011; 43 (02) 127-131
- 2 Briggs TA, Rice GI, Adib N. et al. Spondyloenchondrodysplasia due to mutations in ACP5; A comprehensive survey. J Clin Immunol 2016; 36 (03) 220-234
- 3 Sacri AS, Bruwier A, Baujat G. et al. Childhood-onset autoimmune cytopenia as the presenting feature of biallelic ACP5 mutations. Pediatr Blood Cancer 2017; 64 (02) 306-310
- 4 Schorr S, Legum C, Ochshorn M. Spondyloenchondrodysplasia. Enchondromatomosis with severe platyspondyly in two brothers. Radiology 1976; 118 (01) 133-139
- 5 Renella R, Schaefer E, LeMerrer M. et al. Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: clinical and radiographic delineation of a pleiotropic disorder. Am J Med Genet A 2006; 140 (06) 541-550
- 6 Lausch E, Janecke A, Bros M. et al. Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nat Genet 2011; 43 (02) 132-137
- 7 Crow YJ. Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 2011; 1238: 91-98
- 8 Yu ZX, Song HM. Toward a better understanding of type I interferonopathies: a brief summary, update and beyond. World J Pediatr 2020; 16 (01) 44-51
- 9 Menger H, Kruse K, Spranger J. Spondyloenchondrodysplasia. J Med Genet 1989; 26 (02) 93-99
- 10 Hong SW, Huh KH, Lee JK, Kang JH. Craniofacial anomalies associated with spondyloenchondrodysplasia: two case reports. Medicine (Baltimore) 2018; 97 (50) e13644
- 11 Bilginer Y, Düzova A, Topaloğlu R. et al. Three cases of spondyloenchondrodysplasia (SPENCD) with systemic lupus erythematosus: a case series and review of the literature. Lupus 2016; 25 (07) 760-765
- 12 Crow YJ. Type I interferonopathies: mendelian type I interferon up-regulation. Curr Opin Immunol 2015; 32: 7-12
- 13 Girschick H, Wolf C, Morbach H, Hertzberg C, Lee-Kirsch MA. Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene. Pediatr Rheumatol Online J 2015; 13 (01) 37
- 14 Kulkarni ML, Baskar K, Kulkarni PM. A syndrome of immunodeficiency, autoimmunity, and spondylometaphyseal dysplasia. Am J Med Genet A 2007; 143A (01) 69-75
- 15 Uhlmann D, Rupprecht E, Keller E, Hörmann D. Spondyloenchondrodysplasia: several phenotypes–the same syndrome. Pediatr Radiol 1998; 28 (08) 617-621
- 16 Tüysüz B, Arapoglu M, Ungür S. Spondyloenchondrodysplasia: clinical variability in three cases. Am J Med Genet A 2004; 128A (02) 185-189
- 17 Renella R, Superti-Furga A. A new case of spondyloenchondrodysplasia with immune dysregulation confirms the pleiotropic nature of the disorder: comment on “A syndrome of immunodeficiency, autoimmunity, and spondylometaphyseal dysplasia” by M.L. Kulkarni, K. Baskar, and P.M. Kulkarni [2006]. Am J Med Genet A 2007; 143A (12) 1394-1395
- 18 Kara B, Ekinci Z, Sahin S. et al. Monogenic lupus due to spondyloenchondrodysplasia with spastic paraparesis and intracranial calcification: case-based review. Rheumatol Int 2020; 40 (11) 1903-1910
- 19 Jiang J, Zhao M, Chang C, Wu H, Lu Q. Type I interferons in the pathogenesis and treatment of autoimmune diseases. Clin Rev Allergy Immunol 2020; 59 (02) 248-272
- 20 Ladogana S, Maruzzi M, Samperi P. et al; AIHA Committee of the Italian Association of Paediatric Onco-haematology (AIEOP). Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association. Blood Transfus 2017; 15 (03) 259-267
- 21 Volpi S, Picco P, Caorsi R, Candotti F, Gattorno M. Type I interferonopathies in pediatric rheumatology. Pediatr Rheumatol Online J 2016; 14 (01) 35
- 22 Ramesh J, Parthasarathy LK, Janckila AJ. et al. Characterisation of ACP5 missense mutations encoding tartrate-resistant acid phosphatase associated with spondyloenchondrodysplasia. PLoS One 2020; 15 (03) e0230052
- 23 Miano M, Calvillo M, Palmisani E. et al. Sirolimus for the treatment of multi-resistant autoimmune haemolytic anaemia in children. Br J Haematol 2014; 167 (04) 571-574
- 24 Bride KL, Vincent T, Smith-Whitley K. et al. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood 2016; 127 (01) 17-28
- 25 Miano M, Scalzone M, Perri K. et al. Mycophenolate mofetil and sirolimus as second or further line treatment in children with chronic refractory primitive or secondary autoimmune cytopenias: a single centre experience. Br J Haematol 2015; 171 (02) 247-253