Shwachman Diamond syndrome (SDS) is a rare autosomal recessive genetic disorder and due to its complex and varied clinical manifestations, diagnosis is often delayed. The purpose of this study was to investigate the clinical manifestations and genetic characteristics of SDS in Chinese patients, in order to increase pediatricians\' awareness of SDS and to allow early diagnosis. We conducted a search to identify patients presenting SBDS gene pathogenic variant in two Chinese academic databases. We analyzed and summarized the epidemiology, clinical features, gene pathogenic variants, and key points in the diagnosis and treatment of SDS. We reviewed the clinical data of 39 children with SDS from previously published articles. The interval from the onset of the first symptoms to diagnosis was very long for most of our patients. The age of presentation ranged from 1 day to 10 years (median: 3 months). However, the age of diagnosis was significantly delayed, ranging from 1 month to 14 years (median: 14 months). Hematological abnormalities were the most common presentation, 89.7% (35/39) at the beginning and 94.9% (37/39) at diagnosis of SDS. Diarrhea was the second most common clinical abnormality at the time of diagnosis. 59% (23/39) of patients had a typical history of persistent chronic diarrhea. Furthermore, hepatic enlargement or elevation of transaminase occurred in 15 cases (38.5%). 56.4% patients (22/39) had a short stature, and 17.9% (7/39) patients showed developmental delay. Additionally, twenty patients had compound heterozygous pathogenic variants of c.258 + 2T > C and c.183_ 184TA > CT. Children with SDS in China had high incidence rates of chronic diarrhea, cytopenia, short stature, and liver damage. Furthermore, SBDS c.258 + 2T > C and c.183_ 184TA > CT were the most common pathogenic variants in patients with SDS. The diagnosis of SDS can be delayed if the clinical phenotype is not recognized by the health care provider.

OBJECTIVE: To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene.
METHODS: A female child with SDS who was admitted to the Children\'s Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.
RESULTS: The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. Anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c.258+2T>C and c.100A>G compound heterozygous variants of the SBDS gene. The c.258+2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.100A>G variant was classified as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3).
CONCLUSIONS: The compound heterozygous variants of c.258+2T>C and c.100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS.
We searched the WangFang and China National Knowledge Infrastructure databases with the keywords \"Shwachman-Diamond syndrome,\" \"SDS,\" \"SBDS gene\" and \"inherited bone marrow failure\" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using \"Shwachman-diamond syndrome\" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included.
The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years.
Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.

OBJECTIVE: To explore the characteristics of Shwachman-Diamond syndrome (SDS) in Chinese children in order to provide a reference for early diagnosis.
METHODS: With Shwachman-Diamond syndrome, SDS, SBDS gene and inherited bone marrow failure as the keywords, the search period was set from January 2002 to October 2022. Relevant literature was retrieved from the Wanfang Database and China National Knowledge Infrastructure (CNKI) database. In addition, by using Shwachman-diamond syndrome as a keyword, the search period was also retrieved from the Web of Science, PubMed, and MEDLINE databases from January 2002 to October 2022. A child with SDS treated at the Tongji Hospital was also included. A total of 44 cases with complete clinical data were analyzed with reference to the International Standard for SDS Diagnosis. Chi-square test and t test were used for statistical analysis. Evidence-based research was carried out in the form of systematic review. The epidemiology, clinical characteristics and key points of early diagnosis of the Chinese SDS children were summarized and compared with the international data.
RESULTS: The main characteristics of SDS in Chinese children were summarized as follows: The ratio of males to females was about 1.3 : 1, the median age of onset was 3 months, and the median age of diagnosis was 14 months. The first symptoms were often exocrine pancreatic insufficiency (31.8%) and granulocytopenia with infection (31.8%). According to the international consensus, the incidence rates of the three major diseases of SDS were hemocytopenia (95.4%), pancreatic disease (72.7%), and bone abnormality (40.9%). The common factors underlying SDS disease were variants of the SBDS gene (c.258+2T>C and c.183_184TA>CT), albeit there was no significant correlation between genotype and phenotype (P > 0.05). Compared with international reports, the clinical manifestations and genotypes of Chinese SDS children are different (P < 0.05).
CONCLUSIONS: The SDS children have an early age of onset and significant individual difference. It is necessary to analyze the case-related data to facilitate early recognition, diagnosis and clinical intervention.

报道1例急性双系列白血病，因化疗后血象难以恢复伴胰腺重度脂肪化，行基因检测诊断Shwachman-Diamond综合征。该病临床特征表现为骨髓功能衰竭，胰腺外分泌功能障碍，骨骼异常，恶性肿瘤转化风险，是一种累及多系统的罕见遗传病，需临床医生提高对该病的认识。.

暂无摘要。

Shwachman-Diamond syndrome (SDS) is the second most common cause of exocrine pancreatic insufficiency, and 90% of patients carry mutations in the SBDS gene, the most common being the c.183_184delinsCT and c.258+2T>C variants. However, precise detection of these most contributory variants by conventional short-read next-generation sequencing data analysis is limited because of the SBDS/SBDSP1 highly homologous sequences. In this study, an efficient approach was established to infer the haplotype of SBDS based on the expectation-maximization algorithm. The workflow was retrospectively applied to detect the two most common SBDS variants in a Chinese SDS high-risk cohort, and a systematic comparison of variant detection results was performed between the workflow and conventional next-generation sequencing analysis based on Sanger sequencing validation. Among the Chinese SDS high-risk cohort (n = 47) and their available parents (n = 64), the established workflow improved the diagnostic rate for these two variants by 27.7% (95% CI, 15.6%-42.6%) compared with conventional analysis. For overall variant detection, the established workflow achieved 100% (95% CI, 92.5%-100%) concordance with Sanger sequencing, whereas conventional analysis showed only 65.8% accuracy; these results included 25.2% with missed variant calls, 7.2% with diagnosed but inaccurate variant calls, and 1.8% with false-positive calls. With its favorable result in both SDS patient diagnosis and carrier detection performance, the provided workflow showed its potential in clinical application for SDS molecular diagnosis.

暂无摘要。

暂无摘要。

BACKGROUND: The aim of this study was to analyze the genetic abnormalities and clinical manifestations of Shwachman-Diamond syndrome (SDS).
METHODS: A Chinese infant with elevated transaminase and a novel mutation at of sbdsc.258 +2T>C and c.184a>Tc.292G>A.
METHODS: The female patient was 5 months\' old at onset, with elevated transaminase as the first manifestation accompanied by restricted growth and development and oily stool. After sequencing the blood samples from patients and their parents, the heterozygous mutations of sbdsc.258 +2T>C and c.184a>T were detected.
METHODS: After admission, the patient was provided compound glycyrrhizin, Newtide formula milk supplemented with probiotics, fat-soluble vitamins, oral medication to adjust the spleen and stomach, and other symptomatic treatments.
RESULTS: The stool traits improved, and the levels of liver function transaminases decreased compared with before.
CONCLUSIONS: SDS is a rare disease with a variety of clinical manifestations. Pancreatic exocrine dysfunction, blood system manifestations, and bone abnormalities are common clinical manifestations, and genetic testing is helpful for diagnosis.