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.

The Greek Registry of Shwachman Diamond‐Syndrome: Molecular and clinical data

“…12,17,18 Several types, involving ichthyosiform condition or eczematous eruption have been described and may be attributed to pancreatic failure and subsequent malabsorption of several nutrients, including fat-soluble vitamins, essential fatty acids, and zinc. 13,19,20 This the first report of an SDS patient presenting with plaque psoriasis, which did not respond to treatment with fat-soluble vitamin, indicating a non-nutritional etiology.…”

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants

“…Skin examinations showed eczema, café-au-lait spots, and hypo- or hyperpigmentation. 47 Interestingly, skin findings were common in patients with DNAJC21 , but they were absent in patients with SRP54 and EFL1 . Retinal disease was observed in half of the patients with DNAJC21 disease, but in none of the patients with SRP54 and EFL1 variants.…”

Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature

“…Hypoglycemia was observed as early as 3 months, while neutropenia and pancreatic insufficiency were observed 11 months later. Genetic testing disclosed the presence of SBDS:c.258+2T>C in trans with the novel SBDS:c.284T>G:p.Val95Arg variant possibly leading to an impaired neutral lipid metabolism, most likely occurring in the cytoplasm compartment, analogous to DCS [ 79 ].…”