Case Report Molecular Characterization of a Portuguese Patient with Shwachman-Diamond Syndrome *Rosa M. Lima, †Elı ´sio Costa, *Cristina Rocha, ‡Emı ´lia Vieira, ‡Rosa ´rio dos Santos, †Jose ´ Barbot, and *Herculano Rocha *Servic xo de Pediatria. Hospital Central Especializado de Crianc xas Maria Pia; †Servic xo de Hematologia. Hospital Central Especializado de Crianc xas Maria Pia; ‡Unidade de Gene´tica Molecular. Instituto de Gene´tica Me´dica Dr. Jacinto de Magalha˜es INTRODUCTION Shwachman-Diamond syndrome (SDS) a rare autoso- mal recessive disorder described first time 1964 (1), is characterized by the association of exocrine pancreatic and bone marrow dysfunction. Other systemic findings (skeletal, liver and psychomotor) or problems secondary to bone marrow dysfunction may also be detected (1–4). Intermittent or persistent neutropenia is the most com- mon hematologic finding, but anemia and thrombocyto- penia are present in approximately 40% of the patients (1–4). In 2002, fine mapping identified the locus for SDS in band 7q11. More recently Boocock et al. (5) identified 18 positional candidate genes in this locus and examined eight of them for occurrence SDS-associated changes. They found alterations only in a previously uncharac- terised gene. This gene, designated SBDS (Shwachman- Bodian-Diamond syndrome), is composed of five exons spanning 7.9Kb. The authors also described a pseudogene (SBDSP) with 97% homology to SBDS (5). Only two reports have described mutations in the SBDS gene. The original article described 14 different muta- tions found in 158 SDS families, mostly of European ancestry. The majority of SBDS mutations were found to occur within a 240-bp region around exon 2 and resulted from gene conversion as the result of recombination with the pseudogene (5). In the other report, mutations were identified in four patients; two recurring mutations and three novel changes were found (6). We describe a Portuguese patient with SDS found to be compound heterozygous for two previously described mutations (183–184TA.CT + 201A.G and 258+2T.C). CASE REPORT A 3-year-old boy presented with failure to thrive, diarrhea, developmental delay and neutropenia. His peri- natal history was uneventful. During his third month of life the child was evaluated because of failure to thrive, anaemia and hypotonia. A diagnosis of cytomegalovirus infection was established. During his first 3 years inter- mittent neutropenia was documented, with values ranging from normal to severe (200 3 10 9 /L). Initially increased values of aspartate and alanine aminotransferases later normalized, as did other liver function test values, in- cluding a normal serum bilirubin, g-glutamyl transferase and alkaline phosphatase. Clotting studies were normal. At the time of his referral, height and weight below the fifth percentile was noted with no dysmorphic features. Laboratory investigations included hemoglobin of 10.5 g/dL and a white blood cell count of 4700/mm 3 with a neutrophil count of 1645/mm 3 and a platelet count of 216000/mm 3 . Liver function tests were normal, as was the chloride sweat test. A 72-hour fecal fat collection revealed an abnormally increased fat loss. The fecal elas- tase level was 15.9 mg/g (normal .200 mg/g), consistent with pancreatic failure. The hemoglobin F level was elevated for his age (2.76%) and defective neutrophil mobility was observed (0.3 mm; normal range, 1.23–1.77). Bone marrow aspirate with direct metaphase karyotype study was normal. The skeletal survey revealed a metaphyseal chondrodysplasia of the left hip and rib flaring. Normal growth rate was re-established at the age of 4 years after institution of pancreatic enzyme supple- mentation, and his height and weight attained the 25th percentiles. Molecular analysis of the SBDS gene, after parental consent, was performed by direct sequencing of exon 2, using the primers SBDSEX2F: 5#CTGAGGTTACAGT- GACCCGAGA and SBDSEX2R: 5#CTTTCCTCCAGA- AAAACAGCCT. Results revealed the presence of Address correspondence and reprint requests to Rosa M. Lima, Servic xo de Pediatria, Hospital Central Especializado de Crianc xas Maria Pia, Rua da Boavista, 827, 4050-111 Porto, Portugal. Journal of Pediatric Gastroenterology and Nutrition 41:115–116 Ó July 2005 Lippincott Williams & Wilkins, Philadelphia 115