{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T17:53:34Z","timestamp":1777312414558,"version":"3.51.4"},"reference-count":48,"publisher":"Hamad bin Khalifa University Press (HBKU Press)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025]]},"abstract":"\n Background:<\/jats:bold>\n Schimke immunoosseous dysplasia (SIOD) is a condition marked by spondyloepiphyseal dysplasia (SED), leading to short stature, nephropathy, and T-cell immunodeficiency.\n <\/jats:p>\n \n Case presentation:<\/jats:bold>\n A 15-year-old male was referred to the nephrology clinic with a gradual onset of lower-limb swelling. Clinical examination revealed short stature. Laboratory studies revealed renal impairment and nephrotic-range proteinuria. Kidney biopsy showed global sclerosis in 3 of 28 glomeruli, segmental sclerosis in 16 of 28 glomeruli, and 90% foot-process effacement on electron microscopy. A skeletal survey showed flattened thoracolumbar vertebral bodies, a characteristic feature of SIOD. Flow cytometry revealed a low CD4 count. Whole-exome sequencing confirmed that the proband was homozygous for the p.(R611C) variant in the\n SMARCAL1<\/jats:italic>\n gene. The patient was treated with a calcineurin inhibitor (CNI), angiotensin receptor blockers (ARBs), and prophylactic anticoagulation. Initially, he experienced improvement in serum albumin levels and proteinuria. However, his urine protein and creatinine levels subsequently increased, prompting discontinuation of CNI. The patient progressed to end-stage kidney disease (ESKD) and required hemodialysis 18 months after the initial presentation.\n <\/jats:p>\n \n Discussion:<\/jats:bold>\n This report describes a case of SIOD, a rare multisystem disorder characterized by short stature due to SED and nephrotic syndrome, distinguishing it from other hereditary nephrotic syndromes. The patient presented unusually in adolescence with nephrotic-range proteinuria and skeletal abnormalities, representing a rarely reported juvenile variant. Genetic testing revealed a novel homozygous\n SMARCAL1<\/jats:italic>\n mutation, p.(R611C), which was confirmed in his younger sibling. However, the phenotypic expression differed, reflecting the weak genotype\u2013phenotype correlation in SIOD. Unlike many SIOD cases, our patient did not experience recurrent infections despite abnormal immune parameters, suggesting a milder immunodeficiency and making kidney transplantation with cautious immunosuppression a feasible option. Current therapeutic challenges include the lack of effective disease-specific treatments, limited success with conventional transplantation due to infection and malignancy risks, and emerging but logistically complex approaches such as combined stem-cell and kidney transplantation.\n <\/jats:p>\n \n Conclusion:<\/jats:bold>\n SIOD is a rare genetic disorder with variable presentation and outcomes. Our patient, carrying a novel\n SMARCAL1<\/jats:italic>\n mutation and presenting with juvenile-onset disease, progressed to ESKD but had only mild immune dysfunction, making kidney transplantation a potential treatment option. Early recognition is essential to avoid unnecessary treatments, guide supportive care, and enable timely referral for advanced therapies. Clinicians should consider SIOD in patients presenting with short stature and nephrotic syndrome to optimize outcomes.\n <\/jats:p>","DOI":"10.5339\/qmj.2025.121","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T05:30:29Z","timestamp":1765776629000},"source":"Crossref","is-referenced-by-count":0,"title":["Schimke immunoosseous dysplasia (SIOD): Delayed onset of rare disease and novel variant"],"prefix":"10.5339","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5288-5279","authenticated-orcid":true,"given":"Mostafa","family":"Elshirbeny","sequence":"first","affiliation":[{"name":"Nephrology Division, Medicine Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar*Correspondance: Mostafa Elshirbeny melshirbeny@hamad.qa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Awais","family":"Nauman","sequence":"additional","affiliation":[{"name":"Nephrology Division, Medicine Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar*Correspondance: Mostafa Elshirbeny melshirbeny@hamad.qa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Essa","family":"Abuhelaiqa","sequence":"additional","affiliation":[{"name":"Nephrology Division, Medicine Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar*Correspondance: Mostafa Elshirbeny melshirbeny@hamad.qa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Almalki","sequence":"additional","affiliation":[{"name":"Nephrology Division, Medicine Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar*Correspondance: Mostafa Elshirbeny melshirbeny@hamad.qa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3277","reference":[{"issue":"(2):","key":"B1","series-title":"Nat Genet","first-page":"215\u201320","article-title":"Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous 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kidney transplantation in a 10-year-old girl with Schimke immuno-osseous dysplasia","volume":"27","author":"Finsen\n \nSH","year":"2023"},{"issue":"(24):","key":"B6","series-title":"N Engl J Med","first-page":"2295\u2013302","article-title":"Sequential stem cell-kidney transplantation in Schimke immuno-osseous dysplasia","volume":"386","author":"Bertaina\n \nA","year":"2022"},{"issue":"(1):","key":"B7","series-title":"Mol Genet Genomic Med","first-page":"e1051","article-title":"Effects of consanguinity in a cohort of subjects with certain genetic disorders in Qatar","volume":"8","author":"Ben-Omran\n \nT","year":"2020"},{"issue":"(5 Suppl 5):","key":"B8","series-title":"Kidney Int","first-page":"S241\u201389","article-title":"KDIGO 2025 clinical practice guideline for the management of nephrotic syndrome in children","volume":"107","author":"Kidney Disease: Improving Global Outcomes (KDIGO) Nephrotic Syndrome in Children Work Group","year":"2025;"},{"issue":"(1):","key":"B9","series-title":"J Histochem Cytochem","first-page":"32\u201344","article-title":"Insights into the renal pathogenesis in Schimke immuno-osseous dysplasia: A renal histological characterization and expression analysis","volume":"63","author":"Sarin\n \nS","year":"2015"},{"issue":"(1):","key":"B10","series-title":"Ital J Pediatr","first-page":"11","article-title":"Schimke immunoosseous dysplasia: An ultra-rare disease. a 20-year case series from the tertiary hospital in the Czech Republic","volume":"49","author":"Zieg\n \nJ","year":"2023"},{"issue":"(5):","key":"B11","series-title":"Saudi J Kidney Dis Transpl","first-page":"1188\u201391","article-title":"Galloway-Mowat syndrome - Unusual form of nephrotic syndrome in adolescent","volume":"28","author":"Diwakar\n \nG","year":"2017"},{"key":"B12","series-title":"Neurochem Res","first-page":"723\u201327","article-title":"Human coenzyme Q10 deficiency","volume":"32","author":"Quinzii\n 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\nCF","year":"2000"},{"issue":"(3):","key":"B17","series-title":"Am J Med Genet","first-page":"266\u20139","article-title":"Juvenile variant of Schimke immunoosseous dysplasia","volume":"49","author":"Hashimoto\n \nK","year":"1994"},{"issue":"(5):","key":"B18","series-title":"Saudi J Kidney Dis Transpl","first-page":"987\u201391","article-title":"Schimke immune-osseous dysplasia: A case report","volume":"26","author":"Bakr\n \nA","year":"2015"},{"issue":"(6):","key":"B19","series-title":"Pediatr Nephrol","first-page":"672\u20135","article-title":"Generalized atherosclerosis sparing the transplanted kidney in Schimke disease","volume":"19","author":"L\u00fccke\n \nT","year":"2004"},{"issue":"(20):","key":"B20","series-title":"Genes Dev","first-page":"2415\u201325","article-title":"The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart","volume":"23","author":"Cicca\n 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