title: Shwachman-Diamond syndrome presenting with early ichthyosis, associated dermal and epidermal intracellular lipid droplets, hypoglycemia, and later distinctive clinical SDS phenotype.
abstract: Shwachman-Diamond syndrome (SDS) is a recessive ribosomopathy, characterized by bone marrow failure and exocrine pancreatic insufficiency (ePI) often associated with neurodevelopmental and skeletal abnormalities. The aim of this report is to describe a SDS patient with early ichthyosis associated with dermal and epidermal intracellular lipid droplets (iLDs), hypoglycemia and later a distinctive clinical SDS phenotype. At 3 months of age, she had ichthyosis, growth retardation, and failure to thrive. She had not cytopenia. Ultrasonography (US) showed pancreatic diffuse high echogenicity. Subsequently fasting hypoketotic hypoglycemia occurred without permanent hepatomegaly or hyperlipidemia. Continuous gavage feeding was followed by clinical improvement including ichthyosis and hypoglycemia. After 14 months of age, she developed persistent neutropenia and ePI consistent with SDS. The ichthyotic skin biopsy, performed at 5 months of age, disclosed iLDs in all epidermal layers, in melanocytes, eccrine sweat glands, Schwann cells and dermal fibroblasts. These iLDs were reminiscent of those described in Dorfman-Chanarin syndrome (DCS) or Wolman's disease. Both LIPA and CGI-58 analysis did not revealed pathogenic mutation. By sequencing SBDS, a compound heterozygous for a previously reported gene mutation (c.258 + 2T>C) and a novel mutation (c.284T>G) were found. Defective SBDS may hypothetically interfere as in DCS, with neutral lipid metabolism and play a role in the SDS phenotype such as ichthyosis with dermal and epidermal iLDs and hypoglycemia. This interference with neutral lipid metabolism must most likely occur in the cytoplasm compartment as in DCS and not in the lysosomal compartment as in Wolman's disease. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Pediatric Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scalais
authors.affiliation: Division of Pediatric Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.|Department of Pediatrics, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Connerotte
authors.affiliation: Department of Pediatrics, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
authors.forename: Karine
authors.initials: K
authors.lastname: Despontin
authors.affiliation: Department of Pediatrics, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
authors.forename: Armand
authors.initials: A
authors.lastname: Biver
authors.affiliation: Department of Neuropathology, Institute Born-Bunge and University of Antwerp, Antwerpen, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Ceuterick-de Groote
authors.affiliation: Department of Genetic, Academisch Centrum, Amsterdam, Netherlands.
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.affiliation: Departments of Dermatology and Dermatopathology, Saint-Pierre, Brugmann and HUDERF Hospitals, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Kolivras
authors.affiliation: Department of Dermatology, Centre Hospitalier Emile Mayrisch, Luxembourg, Luxembourg.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hachem
authors.affiliation: Department of Pediatric Neurology and Metabolic, UZBrussel Vrije Universiteit, Brussel, Belgium.
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
mesh_terms: D001855:Bone Marrow Diseases / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000175:diagnosis / Q000503:physiopathology*; D007057:Ichthyosis / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D007223:Infant; D066292:Lipid Droplets / Q000378:metabolism / Q000473:pathology; D008068:Lipomatosis / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype; D000081003:Shwachman-Diamond Syndrome
keywords: epidermal and dermal intracellular lipid droplets; exocrine pancreatic insufficiency; hypoglycemia; ichthyosis; neutropenia; triglycerides