Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene

Girschick, H. J.; Wolf, C; Morbach, Henner; Hertzberg, Christoph; Lee-Kirsch, MA

doi:10.1186/1546-0096-13-s1-p141

Cited by 8 publications

(10 citation statements)

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“…However, variability was observed, with subtle manifestations in some cases, and two patients demonstrating only metaphyseal or vertebral changes. A mild skeletal phenotype, with only ‘discrete metaphyseal changes’ at the wrist was also reported by Girschick et al [ 17 ]. In keeping with this radiological diversity, a height within the normal range, particularly at a young age, does not exclude the diagnosis.…”

Section: Discussionsupporting

confidence: 68%

“…1 A diagram illustrating the distribution of all reported ACP5 pathogenic variants. Below the gene diagram data are shown from this study with number of alleles per variant observed in parentheses; in addition pathogenic variants not identified in this study, but previously reported by Lausch et al [ 8 ] and Girschick et al [ 17 ] are depicted above the gene diagram …”

Section: Resultsmentioning

confidence: 86%

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Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

et al. 2016

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PurposeSpondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.MethodsWe compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.ResultsWe observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.ConclusionsOur data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.

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Section: Discussionsupporting

confidence: 68%

Section: Resultsmentioning

confidence: 86%

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

et al. 2016

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“…Spondyloenchondrodysplasia (SPENCD, OMIM 607944) is a rare autosomal recessive skeletal dysplasia which is characterized with neurological involvement and immune dysfunction (25). SPENCD is an interferonopathy.…”

Section: Discussionmentioning

confidence: 99%

Genetic Disorders With Symptoms Mimicking Rheumatologic Diseases

Akça

Kiper

Demir

et al. 2020

Preprint

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BackgroundMusculoskeletal symptoms may be due to non-inflammatory causes including genetic disorders. We aimed to examine the final genetic diagnosis in patients who had presented with musculoskeletal complaints to rheumatology department.MethodsPatients presenting to the department of pediatric rheumatology and consulted to the genetic department between January 2015 and May 2019 were evaluated retrospectively. ResultsA total of 60 patients, 19 boys (31.66%), with a mean age 12.46 ± 1.41 years were included in the study. Total consanguinity rate was 25%. The most common (29.5%) cause of referral to the genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one third of the patients (n: 19) were diagnosed and followed up by the genetic department. The diagnoses of patients were as follows; CACP syndrome (n:3), trichorhinophalangeal syndrome (n:1), progressive pseudoromatoid dysplasia (n:2), LIG4 syndrome (n:1), H syndrome (n:1), SPENCD syndrome (n:3), and nonspecific connective tissue disease (n:8).ConclusionsIn the differential diagnosis of patients who are referred to the department of pediatric rheumatology with complaints of the musculoskeletal system, genetic disorders should also be taken into consideration.Clinical Trial Registration: Hacettepe University Ethics Commission (Approval number: GO 19/781)

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“…SPENCD (OMIM 607944) is a rare autosomal recessive skeletal dysplasia, characterized by neurological involvement and immune dysfunction (26). SPENCD is a member of the interferonopathy group.…”

Section: Discussionmentioning

confidence: 99%

Genetic Disorders With Symptoms Mimicking Rheumatologic Diseases: A Single-Center Retrospective Study

Akça

Kiper

Demir

et al. 2020

Preprint

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BackgroundMusculoskeletal symptoms may be due to noninflammatory causes, including genetic disorders. We aimed to examine the final genetic diagnosis in patients who presented with musculoskeletal complaints to the rheumatology department.MethodsPatients who presented to the Department of Pediatric Rheumatology and were referred to the pediatric genetic department between January 2015 and May 2019 were evaluated retrospectively. ResultsA total of 60 patients, 19 boys (31.66%), with a mean age of 12.46 ± 1.41 years were included in the study. The total consanguinity rate was 25%. The most common (29.5%) cause of referral to the pediatric genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one-third of the patients (n: 19) were diagnosed and followed up by the pediatric genetics department. The diagnoses of patients were as follows: camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome (n: 3); trichorhinophalangeal syndrome (n: 1); progressive pseudorheumatoid dysplasia (n: 2); LIG4 syndrome (n: 1); H syndrome (n: 1); spondyloenchondrodysplasia (SPENCD) (n: 3); and nonspecific connective tissue disorders (n: 8).ConclusionsIn the differential diagnosis of patients who are referred to the Department of Pediatric Rheumatology with complaints of the musculoskeletal system, genetic disorders should also be considered.

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Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene

Cited by 8 publications

References 0 publications

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Genetic Disorders With Symptoms Mimicking Rheumatologic Diseases

Genetic Disorders With Symptoms Mimicking Rheumatologic Diseases: A Single-Center Retrospective Study

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