Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Known genetic defects currently account for only a small proportion of patients meeting criteria for 'probable' or 'possible' common variable immunodeficiency (CVID). A 59-year-old male with a 12-year history of CVID on intravenous immunoglobulin (IVIG) is presented who developed bronchiectasis, cytopenias and malabsorption that are recognized complications of CVID. Work-up for his malabsorption suggested the possibility of Shwachman-Diamond syndrome, confirmed by mutation testing. With the identification of the molecular defect in Shwachman-Diamond syndrome (SDS), it is becoming clear that not all SDS patients have the prominent features of neutropenia or pancreatic malabsorption. A meta-analysis of published immunological defects in SDS suggests that four of 14 hypogammaglobulinaemic SDS patients meet criteria for 'possible' CVID. Mutations in the SBDS gene may therefore be the fifth identified molecular defect in CVID.
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PMID:Some cases of common variable immunodeficiency may be due to a mutation in the SBDS gene of Shwachman-Diamond syndrome. 1819 Jun 2

Shwachman-Diamond syndrome is a rare autosomal recessive disorder caused by mutations in the SBDS gene. The cardinal symptoms arise from exocrine pancreatic insufficiency and bone marrow dysfunction. These lead to malabsorption and haematological abnormalities, susceptibility to infections and to increased risk of leukaemia. Skeletal involvement presents as growth failure, metaphyseal dysplasia and osteoporosis. The majority of patients also have liver dysfunction, learning difficulties and oral and dental problems. Although the disease typically presents in early childhood, phenotypic features change over time and the diagnosis becomes more challenging.
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PMID:[Shwachman-Diamond syndrome--a diagnostic challenge]. 2080 90

Shwachman-Diamond-Bodian syndrome (SDS) is a pleiotropic disorder in which the main features are bone marrow dysfunction and pancreatic insufficiency. Skeletal changes can occur, and in rare cases manifest as severe congenital thoracic dystrophy. We report a newborn boy with asphyxia, narrow thorax, and severe hypotonia initially suggesting a neuromuscular disease. The muscle biopsy showed myopathic changes with prominent variability in muscle fiber size and abnormal expression of developmental isoforms of myosin. The myofibrils showed focal loss and disorganization of myofilaments, and thickening of the Z-discs including some abortive nemaline rods. The boy became permanently dependent on assisted ventilation. Pancreatic insufficiency was subsequently diagnosed, explaining the malabsorption and failure to thrive. Except transitory thrombocytopenia and leukopenia, no major hematological abnormalities were noted. He had bilateral nephrocalcinosis with preserved renal function. Transitory liver dysfunction with elevated transaminase levels and parenchymal changes on ultrasound were registered. The clinical diagnosis was confirmed by detection of compound heterozygous mutations in SBDS using whole-exome sequencing: a recurrent intronic mutation causing aberrant splicing (c.258+2T>C) and a novel missense variant in a highly conserved codon (c.41A>G, p.Asn14Ser), considered to be damaging for the protein structure by in silico prediction programs. The carrier status of the parents has been confirmed. This case illustrates the challenges in differential diagnosis of pronounced neonatal hypotonia with asphyxia and highlights the muscular involvement in SDS. To our knowledge, this is the first report of myopathy evidenced in a patient with clinically and molecularly confirmed SDS.
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PMID:Novel myopathy in a newborn with Shwachman-Diamond syndrome and review of neonatal presentation. 2686 30

Shwachman-Diamond syndrome (SDS) is a rare multisystem ribosomal biogenesis disorder characterized by exocrine pancreatic insufficiency, hematologic abnormalities and bony abnormalities. About 90% of patients have biallelic mutations in SBDS gene. Three additional genes-EFL1, DNAJC21 and SRP54 have been reported in association with a SDS phenotype. However, the cause remains unknown for ~10% of patients. Herein, we report a 6-year-old Chinese boy, who presented in the neonatal period with pancytopenia, liver transaminitis with hepatosplenomegaly and developmental delay, and subsequently developed pancreatic insufficiency complicated by malabsorption and poor growth. Exome sequencing identified a novel de novo heterozygous variant in EIF6 (c.182G>T, p.Arg61Leu). EIF6 protein inhibits ribosomal maturation and is removed in the late steps of ribosomal maturation by SBDS and EFL1 protein. Given the interaction of EIF6 with SBDS and EFL1, we postulate heterozygous variants in EIF6 as a novel cause of Shwachman-Diamond-like phenotype. We compared the phenotype of our patient with those in patients with mutation in SBDS, EFL1, DNAJC21, and SRP54 genes to support this association. Identification of more cases of this novel phenotype would strengthen the association with the genetic etiology.
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PMID:Heterozygous missense variant in EIF6 gene: A novel form of Shwachman-Diamond syndrome? 3265 13