Monogenic lupus due to spondyloenchondrodysplasia with spastic paraparesis and intracranial calcification: case-based review

Kara, Bülent; Ekinci, Zelal; Şahin, Sezgin; Güngör, Mesut; Güneş, Ayfer Sakarya; Öztürk, Kübra; Adroviç, Amra; Çefle, Ayşe; İnanç, Murat; Gül, Ahmet; Kasapçopur, Özgür

doi:10.1007/s00296-020-04653-x

Cited by 23 publications

(21 citation statements)

References 40 publications

(68 reference statements)

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“…It has also been shown that increased osteopontin has an important role in the pathogenesis of albuminuria by acting on renal podocytes, as shown in diabetic patients (possibly increasing glomerular damage through TGF-beta expression) 21 . In addition, since clinical findings may occur at different ages in the same family, even in patients with the same ACP5 gene mutation 22 , immunological and skin findings related to SLE may occur in our patients in the coming years.…”

Section: Discussionmentioning

confidence: 86%

Spondyloenchondrodysplasia Due to Mutation in ACP5 Gene Presenting with Nephrotic Syndrome: A Case Report

Polat

Özdemir

2022

Aktuelle Rheumatologie

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Spondyloenchondrodysplasia (SPENCD) with immune dysregulation (SPENCDI) is a rare autosomal recessive inherited immuno-osseous dysplasia characterized by spondylo-metaphyseal enchondromas, along with immune dysregulation ranging from immunodeficiency to autoimmune disorder. Here, we present two cousins with ACP5 gene mutation who had severe short stature with mild hypogammaglobulinemia, nephrotic syndrome, autoimmune thyroiditis and cerebral calcification (Case 1); and in the other (Case 2), there was no clinical findings other than severe short stature, CD4+−T cell lymphopenia and non-autoimmune compensated hypothyroidism. We wanted to emphasize that monogenic causes should be considered in the etiology of early-onset nephrotic syndrome due to the detection of a mutation in the ACP5 gene (her actual diagnosis was changed to SPENCDI.) 5 years after the diagnosis of nephrotic syndrome in the first case, and that the renal involvement may occur without SLE in patients with ACP5 mutation. Severe short stature was a common finding in both cases. We underlined that the clinic can be different even in the same mutation, due to the absence of cerebral calcification and renal involvement in the second case, which is a cousin with Case 1. As a result, endocrinologists, immunologists, rheumatologists, nephrologists and orthopedists should be aware of this syndrome, because SPENCDI causes a pleiotropic (due to more than one phenotypic effect of a gene) clinical picture. Severe short stature may be the only presenting sign of patients with SPENCDI. In addition, in the presence of early-onset nephrotic syndrome and autoimmune thyroiditis, the patient should be evaluated for this type of monogenic disorders as well.

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Section: Discussionmentioning

confidence: 86%

Spondyloenchondrodysplasia Due to Mutation in ACP5 Gene Presenting with Nephrotic Syndrome: A Case Report

Polat

Özdemir

2022

Aktuelle Rheumatologie

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“…A wide spectrum of immune dysregulation associated with SPENCDI has been described, including development of SLE. Neurological manifestations include developmental delay, spastic paresis, and intracranial calcifications ( 149 ). Mutations in PSMB8 is a cause of a disorder previously called chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE).…”

Section: Autoinflammatory Disordersmentioning

confidence: 99%

Neuroinflammation Associated With Inborn Errors of Immunity

Lindahl

Bryceson

2022

Front. Immunol.

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The advent of high-throughput sequencing has facilitated genotype-phenotype correlations in congenital diseases. This has provided molecular diagnosis and benefited patient management but has also revealed substantial phenotypic heterogeneity. Although distinct neuroinflammatory diseases are scarce among the several thousands of established congenital diseases, elements of neuroinflammation are increasingly recognized in a substantial proportion of inborn errors of immunity, where it may even dominate the clinical picture at initial presentation. Although each disease entity is rare, they collectively can constitute a significant proportion of neuropediatric patients in tertiary care and may occasionally also explain adult neurology patients. We focus this review on the signs and symptoms of neuroinflammation that have been reported in association with established pathogenic variants in immune genes and suggest the following subdivision based on proposed underlying mechanisms: autoinflammatory disorders, tolerance defects, and immunodeficiency disorders. The large group of autoinflammatory disorders is further subdivided into IL-1β-mediated disorders, NF-κB dysregulation, type I interferonopathies, and hemophagocytic syndromes. We delineate emerging pathogenic themes underlying neuroinflammation in monogenic diseases and describe the breadth of the clinical spectrum to support decisions to screen for a genetic diagnosis and encourage further research on a neglected phenomenon.

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“…1 Vasculitis, renal involvement and autoimmune hypothyroidism are also reported as a continuum of this spectrum. 4,5 Immune dysregulation predisposes to an immunodeficient state characterized by hypogammaglobulinemia and low B-, T-and NK-cell counts causing recurrent pneumonia, disseminated herpes zoster and skin and dental abscesses. 6 Neurological manifestations include developmental delay, spasticity, ataxia, psychosis, abnormal movements and painful multifocal neuropathy.…”

Section: Letter To the Editormentioning

confidence: 99%