P790: Identification of a balanced rearrangement of 22q11.2 in a family with a history 22q11.2 microduplication and microdeletion syndromes

Treatment and Management: We opted for lifestyle measures and physical therapy for symptomatic relief owing to the already elevated 1,25-dihydroxyvitamin D. Outcome and Follow-Up: The patient continues to follow the lifestyle measures; however, improvement is minimal due to the complex presentation.Discussion: Misdiagnosis of hypophosphatemic rickets in low-and middle-income countries (LMICs) settings often results from limited access to genetic testing and advanced metabolic evaluations, leading to delayed diagnosis or inappropriate management.In such settings, early presentations are often mistaken for nutritional deficiencies, which can eventually evolve into complex cases with long-term complications, as described in this case.Emerging evidence suggests that patients with autosomal recessive hypophosphatemic rickets/osteomalacia are at a high risk of diffuse skeletal hyperostosis and ligament ossification, as seen in our case, in contrast to XLH.Moreover, the discovery of a novel DMP1 variant expands the variant spectrum and emphasizes the need to consider hypophosphatemic rickets in differential diagnoses.Limited access to genetic diagnostics in LMICs underscores the importance of enhancing diagnostic capabilities.Treatment data for autosomal recessive hypophosphatemic rickets/osteomalacia is limited, and response to therapies for FGF23-mediated hypophosphatemia, such as activated vitamin D, phosphate supplementation, or Burasumab, remains unclear, and there is insufficient evidence to initiate this treatment. Conclusion:The novel DMP1 variant discovered in this case highlights the need to explore management options through clinical trials to improve care.Molecular diagnosis is required for accurate and timely identification of hypophosphatemic osteomalacia.Introduction: Hypophosphatemic Osteomalacia refers to a group of rare bone diseases, with X-linked hypophosphatemia (XLH) being the most common form, while autosomal dominant or recessive forms being rare entities.We describe severe autosomal recessive hypophosphatemic osteomalacia with osteosclerosis and hyperostosis associated with skeletal deformity, short stature, enthesopathy, and tooth loss in a middle-aged woman.Case Presentation: A 46-year-old woman presented to the Aga Khan University Hospital, Karachi, Pakistan with a five-year history of progressive joint stiffness.Her history revealed rickets, diagnosed and treated as vitamin D dependent at 8 months of age.Corrective surgeries were conducted later in life.There was no history of similar disorder in the family.Investigations were consistent with hypophosphatemia, normal calcium, PTH, and vitamin D. X-rays showed increased bone density in lumbosacral, lower extremity and cervical spine with calcification of posterior spinal and bilateral sacrospinous ligaments.MRI spine identified multilevel facet arthropathy, ligamentum flavum hypertrophy, disc bulges and spinal canal neural foraminal narrowing.DXA scans showed significantly elevated Z-scores in the left forearm, lumbar spine, and left total hip.On examination, she had a short stature, without proximal myopathy.Multiple dental extractions were noted with dental bridge in left lower jaw with no evidence of dental caries or dental abscess.Diagnostic Workup: A comprehensive metabolic evaluation confirmed renal phosphate leak at a TRP 83.72, TmP/GFR of 1.8 mg/dL and FePO 4 of 16.2% at a serum phosphate level of 1.8 mg/dL.Serum calcium was 9 mg/dL and FeCa was 0.45%, 25-hydroxyvitamin D was 52.3 ng/mL and 1,25-dihydroxyvitamin D was high at 138 pg/ml.Skeletal survey showed generalized osteosclerosis of the skull with hyperostosis frontalis, multiple large osteophytes in the cervical spine, and ligamentous ossification in the lumbar spine and pelvis including paravertebral and sacrospinal ligament and osteophyte formation with enthesopathy.No evidence of sandwich vertebra or bone within bone appearance was seen.A comprehensive 358-gene skeletal disorder panel revealed a novel homozygous splice site variant of uncertain significance (VUS) in Intron 5 of DMP1 gene (OMIM 600980, HGNC