Shwachman-Diamond syndrome: first molecular diagnosis in a Brazilian\nchild
A 6-year-old boy was diagnosed with cystic fibrosis at the age of 15 months due to\nrecurrent respiratory infections, diarrhea and therapeutic response to pancreatic\nenzymes. Three sweat tests were negative.\nAt the age of 5 years, the patient began to experience pain in the lower limbs, laxity\nof joints, lameness and frequent falls. There was no history of fractures, liver or\nkidney disease, use of medications associated with osteoporosis or rickets, lack of\nsunlight exposure, low calcium or vitamin D diet, or reports of metabolic bone disease\nor bone dysplasia in the family. There is no evidence for consanguinity. On physical\nexamination his weight was 16 kg (10th centile), height 103 cm (5-10th centile), with\nP1/G1 Tanner pubertal stage. The liver was palpable 3 cm below the right costal margin.\nHe also presented discrete genu varum, hyperextensible elbow joints and increased\nanteroposterior diameter of thorax. Review of medical records showed chronic leukopenia\n(leukocytes: 3.1-3.5 x 103/µL), neutropenia (segmented neutrophils: 15-22%),\nbut normal hemoglobin, hematocrit, and platelet count. A radiological study showed\nmetaphyseal chondrodysplasia, sclerosis and pseudocysts in radial, humeral, ulnar,\ntibial and femoral metaphysis (). Bone\ndensitometry showed a z-score of -1.6.\nEvaluation of serum calcium, phosphorus, alkaline phosphatase, 25(OH)Vitamin D,\n1,25(OH)Vitamin D, parathyroid hormone, liver and kidney function, thyroid function,\nelectrolytes, lipase, amylase, blood sugar, immunoglobulin (IgG, IgA and IgM) and CD4\nand CD8 lymphocyte counts were all normal. Hemoglobin electrophoresis showed: Hemoglobin\n(Hb) A1: 91.7%; Hb A2: 2.6%; Hb F: 5.7%. Blood sugar, insulin and an oral glucose\ntolerance test were normal, in spite of a raised glycated hemoglobin level of 6.5%\n(normal: < 5.6%). Fecal fat excretion tested positive and an abdominal ultrasound\nrevealed increased pancreatic echogenicity. Sanger sequencing( demonstrated\nknown pathogenic mutations in exon 2 of the SBDS gene: 183-184TA - CT K62X (Stop codon\nno exon 2) and 258+2T-C transition. In addition, a non-pathologic silent nucleotide A to\nG transition at position 201 in the SBDS gene was also detected in heterozygosis.