Schimke immuno-osseous dysplasia. A case report in Colombia

Abstract

Background: Schimke immune-osseous dysplasia (SIOD) is an ultra-rare multisystemic, monogenic, and autosomal recessive inherited disease caused by biallelic mutations in the SMARCAL1 gene. Approximately 100 cases have been reported worldwide. The disease is characterized by skeletal, renal, and immunological abnormalities.

Case description: This is a 6-year-old female patient who debuted with nephrotic syndrome at five years of age, with a switch to corticosteroid resistance and poor response to immunosuppressive treatment received. The patient was admitted and referred to our institution due to convulsive status. During her hospitalization, thrombosis was found in the left renal vein, and a renal biopsy report of Collapsing Focal and Segmental Glomerulosclerosis (FSGS) was obtained. The patient had multiple infections during hospitalization, with T lymphocyte lymphopenia and severe IgG hypogammaglobulinemia. Additionally, given dysmorphic facies, delayed weight-height development, and spondyloepiphyseal dysplasia, exome sequencing was performed, finding an homozygous pathogenic variant c.1933C > T p.Arg645Cys in SMARCAL1, compatible with the diagnosis of SIOD.

Discussion: We present the case of a patient that exhibited a severe phenotype of the disease, with skeletal, renal, severe combined immunological compromise and cerebrovascular involvement during follow-up, and the available proposed mechanisms of the disease focused on the clinical manifestations of this patient. It is the first case of SIOD reported in Colombia and the first comprehensive characterization reported in the literature of a patient with homozygosity of the known variant c.1933C > T p.Arg645Cys.

Conclusion: A severe phenotype of the disease with cerebrovascular involvement by homozygosity of the known variant c.1933C > T p.Arg645Cys in the SMARCAL1 gene can be expected.

Keywords: Children; Focal segmental glomerulosclerosis; Nephrotic syndrome; Primary immunodeficiency disease; Schimke immunoosseous dysplasia.

Fig. 1

Light microscopy of the patient's kidney biopsy. a. Periodic acid-Schiff stain (4×). In the sample, a total of 61 glomeruli were identified, and none of them exhibited global sclerosis. In 9 (14%) glomeruli, segmental sclerosis was observed, out of which 3 displayed a collapsing pattern associated with hyperplasia, podocyte hypertrophy, and protein reabsorption drops. Some glomeruli showed mesangial expansion and hypercellularity without alterations in the glomerular basement membrane. Hyaline casts and signs of mild acute tubular injury were noted in tubules. Mild tubular atrophy and interstitial fibrosis without associated interstitial inflammation were observed. In peritubular arteries, arterioles and capillaries, no significant alterations were detected. b. Jones methenamine silver stain (40×). Glomerulus with retraction and collapse of the capillary loops associated with hyperplasia and podocyte hypertrophy. This photo was taken by Dr. Nancy Janeth Vargas Parra.

Fig. 2

Photograph of the patient and radiographs of the spine and hip. a. Prominent cheeks, hirsutism, short neck and thorax, and globular abdomen are observed. b. The arrow marks the spondyloepiphyseal dysplasia with flattening and oval margins in the vertebral bodies. c. The arrows mark the dysplasia of the acetabulum (bilaterally flat and shallow) and femoral heads (bilaterally moved upwards).

Fig. 3

Timeline of the events in the case.