Introduction: Adolescence is a crucial period for achieving peak bone mass. Risk factors such as chronic inflammation, endocrine issues, corticosteroid use, and extended immobility can lead to severe secondary osteoporosis and fragility fractures. Case: A 15-year-old female with transfusion-dependent thalassemia had been hospitalized for over a year following severe acute gastroenteritis complicated by septic shock, multiorgan failure, and secondary hemophagocytic lymphohistiocytosis (HLH). She received pulse methylprednisolone therapy for HLH, which was tapered over 6 months. Her clinical course was further complicated by critical illness polyneuropathy and post-infectious bronchiectasis, leading to ventilator dependence and a bedbound state. During regular physiotherapy sessions, she developed a sudden onset of severe left shoulder pain. A radiograph of the left shoulder revealed a closed fracture of the humeral neck. Biochemical evaluation showed normal serum calcium and phosphate levels, adequate vitamin D status, and normal alkaline phosphatase levels. However, follicle-stimulating hormone, luteinizing hormone (LH), and estradiol levels were undetectable, consistent with arrested puberty due to chronic illness. A bone mineral density scan showed a lumbar spine Z-score of −6, indicating severe osteoporosis. She was started on intravenous zoledronate for secondary osteoporosis, and physiotherapy was resumed to improve musculoskeletal strength. Conclusion This patient was treated with bisphosphonate therapy for severe secondary osteoporosis caused by multiple risk factors, including chronic illness, prolonged immobility, corticosteroid use, and hypogonadotropic hypogonadism, with limited potential for spontaneous bone recovery. This case highlights the importance of early endocrine monitoring and bone health assessments to identify impaired bone growth and prevent fragility fractures in high-risk adolescents.
Adolescent ; Humans ; Chronic Disease ; Thalassemia

Introduction: RENI syndrome (renal, endocrine, neurologic, and immune syndrome), also known as sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS), is a rare autosomal recessive disorder caused by pathogenic variants in the SGPL1 gene. This gene encodes sphingosine-1- phosphate lyase, an enzyme responsible for the final step in sphingolipid degradation. Impaired enzyme activity results in the accumulation of sphingolipid intermediates, leading to multisystem involvement affecting the kidneys, adrenal glands, skin, immune system, and nervous system. Frequently reported manifestations include steroid-resistant nephrotic syndrome, primary adrenal insufficiency, ichthyosis, and neurological abnormalities. Case: We report a 15-year-old male with a history of primary adrenal insufficiency diagnosed at age three after presenting with recurrent vomiting and abdominal pain. He was started on steroid replacement therapy and remained stable without episodes of adrenal crisis. He also had ichthyosis requiring dermatological follow-up. During routine surveillance, persistent proteinuria was detected, and urinary protein excretion increased over time. Ultrasound showed renal parenchymal changes despite preserved renal function. Whole-exome sequencing identified a homozygous variant of uncertain significance in the SGPL1 gene, consistent with RENI syndrome. He was started on enalapril for his proteinuria and continues to undergo multidisciplinary follow-ups. Both parents are consanguineous, but were not screened. Mutations in SGPL1 have increasingly been recognized as a monogenic cause of syndromic steroid-resistant nephrotic syndrome, associated with endocrine and dermatological features. Renal histopathology in cases reported often shows focal segmental glomerulosclerosis, reflecting podocyte injury due to disruption of sphingolipid signaling pathways. Early recognition is crucial, as patients need multidisciplinary care. Conclusion This case highlights the importance of considering RENI syndrome in patients presenting with early-onset primary adrenal insufficiency accompanied by renal and dermatological symptoms. Increased clinical awareness and prompt genetic testing can enable earlier diagnosis, guide long-term monitoring, and support appropriate genetic counseling.
Adrenal Insufficiency ; Proteinuria ; Ichthyosis