Shwachman-Diamond syndrome: first molecular diagnosis in a Brazilian child

Abstract

Herein the first molecular diagnosis of a Brazilian child with Shwachman-Diamond Syndrome is reported. A 6-year-old boy was diagnosed with cystic fibrosis at the age of 15 months due to recurrent respiratory infections, diarrhea and therapeutic response to pancreatic enzymes. Three sweat tests were negative. At the age of 5 years, he began to experience pain in the lower limbs, laxity of joints, lameness and frequent falls. A radiological study revealed metaphyseal chondrodysplasia. A complete blood cell count showed leukopenia (leukocytes: 3.1-3.5 x 103/µL), neutropenia (segmented neutrophils: 15-22%), but normal hemoglobin, hematocrit and platelet count. A molecular study revealed biallelic mutations in the Shwachman-Bodian-Diamond Syndrome gene (183-184TA-CT K62X in exon 2 and a 258+2T-C transition) confirming the diagnosis of Shwachman-Diamond Syndrome. A non-pathologic, silent nucleotide A to G transition at position 201 was also found in heterozygosis in the Shwachman-Bodian-Diamond Syndrome gene. This is the first report to describe a Brazilian child with molecular diagnosis of Shwachman-Diamond Syndrome, a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, intermittent or persistent neutropenia and skeletal changes. Other characteristics include immune system, hepatic and cardiac changes and predisposition to leukemia. Recurrent bacterial, viral and fungal infections are common. The possibility of Shwachman-Diamond Syndrome should be kept in mind when investigating children with a diagnosis of cystic fibrosis and normal sweat tests.

Shwachman–Diamond syndrome: Nationwide survey and systematic review in Japan

“…We searched three electronic databases to identify the relationship between medical treatment and prognosis of SDS patients. On PubMed, 24 articles were identified, consisting of a clinical practice guideline, two case series, six case reports, and 15 reviews . On ICHUSHI, 13 articles were identified: two case reports and 11 reviews .…”

“…In these reports, pancreatic enzyme replacement therapy, fat‐soluble vitamins and trace element supplementation, parenteral nutrition therapy and intake of MCT formula were performed as medical interventions, and these treatments often improved the condition of malabsorption and provided relief from steatorrhea and diarrhea in several reports . Pichler et al .…”

“…In the present systematic review, we obtained clinical information on 46 patients in two case series and eight case reports . The age range was 0.25–19 years old.…”

“…Pancreatic exocrine insufficiency was noted in 39 patients; 43 patients had pancreatic enzyme replacement; and nine patients had fat‐soluble vitamin supplementation. While only three reports mentioned improvement in malabsorption and stools, most reports did not refer to prognosis. In the Pichler et al .…”

“…When the two reviewers had different opinions that could not be resolved by discussion, a third person was invited to make a final decision. We ultimately identified 37 studies addressing the medical treatment for malabsorption or prognosis in SDS . The strength of evidence for each study was determined according to the Medical Information Network Distribution Service ( MINDS) Handbook for Clinical Practice Guideline Development 2014 of the Japan Council for Quality Health Care, and Grading of Recommendations Assessment, Development and Evaluation (GRADE), and an evidence table constructed …”