Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Indian J Pediatr. 2021 Aug;88(8):819-823. doi: 10.1007/s12098-020-03636-x. Epub 2021 Mar 13.
Monogenic disorders causing systemic lupus erythematosus represent a small subset of cases. Type-1 interferonopathies, like spondyloenchondrodysplasia with immune dysregulation constitute an important functional category of monogenic lupus. Apart from autoimmune disorders, neurological and skeletal abnormalities are additional manifestations observed in this disorder. A young female presented with seizures due to acute hemorrhagic stroke secondary to malignant hypertension. On evaluating the cause for hypertension, there was evidence of glomerulonephritis and multiple autoantibodies positivity including dsDNA. A diagnosis of lupus was made based on clinical and laboratory findings. Kidney biopsy revealed mesangial proliferative glomerulonephritis with predominant IgA deposits favouring IgA nephropathy. Additional features in the form of short stature with vertebral abnormalities and bilateral basal ganglia calcification led to evaluation of Type-1 interferonopathies. Sanger sequencing identified a novel compound heterozygous variants c.550C>T (p.Q184*) in exon 3 and c.740T>G (p.L247R) in exon 4 of ACP5 gene. Parents were found to be carriers of the variants in ACP5 gene. Management included antihypertensive agents and symptomatic therapy. On follow-up, there was complete resolution of glomerulonephritis and normalization of blood pressure. This case report documents the classic phenotype comprising autoimmune, skeletal, and neurological abnormalities in spondyloenchondrodysplasia with immune dysregulation with a novel variant on Sanger sequencing in an Indian patient. This report also highlights the rare coexistence of IgA nephropathy in monogenic lupus.
单基因疾病引起的系统性红斑狼疮占少数病例。1 型干扰素病，如伴有免疫失调的脊椎骨骺发育不良，构成了单基因狼疮的一个重要功能类别。除了自身免疫性疾病，神经系统和骨骼异常是该疾病的其他表现。一名年轻女性因恶性高血压继发急性出血性中风而出现癫痫发作。在评估高血压的病因时，发现有肾小球肾炎的证据和多种自身抗体阳性，包括 dsDNA。根据临床和实验室发现，诊断为狼疮。肾脏活检显示局灶节段性肾小球肾炎，伴系膜增生，IgA 沉积为主，支持 IgA 肾病。身材矮小、椎体异常和双侧基底节钙化等额外特征导致 1 型干扰素病的评估。桑格测序在 ACP5 基因的外显子 3 中发现了一个新的复合杂合变体 c.550C>T（p.Q184*），在外显子 4 中发现了 c.740T>G（p.L247R）。父母被发现是 ACP5 基因变异的携带者。治疗包括抗高血压药物和对症治疗。随访时，肾小球肾炎完全缓解，血压正常化。该病例报告记录了伴有免疫失调的脊椎骨骺发育不良的经典表型，包括自身免疫、骨骼和神经系统异常，在印度患者中通过桑格测序发现了一种新的变异。该报告还强调了单基因狼疮中 IgA 肾病的罕见共存。
