LAUSR

A 12-year-old normally developing girl presented with progressive pallor for the last 2-months. She also had slowly progressive decreased vision in her bilateral visual fields. There was no history of double vision, headache, photopsia, seizures, focal neurological deficit, and bowel and bladder impairment. She received three blood transfusions in the past 3-years. There was no history of, jaundice, bleeding from any site and rashes. She was born to nonconsanguineous parents and there was a history of the death of five siblings (both male and female) in infancy, due to severe anaemia and multiple life-threatening infections. On neurological examination, her visual acuity was 20/40 in both the eyes, and she correctly identified 11 of Ishihara colour plates by both the eyes. Her fundoscopic examination showed bilateral optic atrophy. She also had severe pallor, tachypnoea, tachycardia and massive splenomegaly. Investigations revealed pancytopenia. Peripheral smear showed normocytic, normochromic red blood cells and the absence of any malignant blast cells. X-ray of humerus showed characteristic ‘bone-in bone’ appearance (Fig. 1). She also had bilateral moderate conductive hearing loss, hypocalcemia, normal serum phosphate, and increased alkaline phosphatase level, low vitamin D level (17 nmol/L; normal range: 50–100 nmol/ L) and raised parathyroid hormone levels (162 ng/L, normal range: 10–65 ng/L). Magnetic resonance imaging of the brain showed compression in the optic canal due to a scalloped inner table (Fig. 2). The visual evoked response showed elevated P100 latencies in both the eyes. Bone marrow trephine biopsy revealed obliterated marrow space, with hypocellularity, suppressed erythropoiesis, granulopoiesis, and megakaryocytes, along with thick, disorganised bony trabeculae. Massively parallel sequencing revealed a heterozygous missense likely pathogenic variant (c.1225C>T, p.Arg409Trp) in