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

Abstract

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis, resulting in short stature. SPENCD often coexists with neurologic disorders and immune dysregulation. Spasticity, developmental delay and intracranial calcification are main neurologic abnormalities. Large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes. SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. We present two siblings, 13-year-old girl and 25-year-old boy with SPENCD, from consanguineous parents. Both patients had short stature, platyspondyly, metaphyseal changes, spastic paraparesis, mild intellectual disability, and juvenile-onset SLE. The age at disease-onset was 2 years for girl and 19 years for boy. Both had skin and mucosa involvement. The age at diagnosis of SLE was 4 years for girl, and 19 years for boy. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. Juvenile-onset SLE accounts for about 15-20% of all SLE cases. But, the onset of SLE before 5-years of age and also monogenic SLE are rare. Our case report and the literature review show the importance of multisystemic evaluation in the diagnosis of SPENCD and to remind the necessity of investigating the monogenic etiology in early-onset and familial SLE cases.

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

“…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.…”

Neuroinflammation Associated With Inborn Errors of Immunity

“…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).…”

Spondyloenchondrodysplasia with immune dysregulation: Role of sirolimus

“…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.…”