China
Africa
Explore chapters and articles related to this topic
Hematological problems in the neonate
Published in Prem Puri, Newborn Surgery, 2017
Andrea M. Malone, Owen P. Smith
Shwachman–Diamond syndrome (SDS) usually presents with isolated neutropenia that may progress to bone marrow failure. It is characterized by exocrine pancreatic insufficiency leading to malabsorption and steatorrhea in the first few months of life. Infants develop growth retardation, frequent bacterial infections, and failure to thrive. They have pathognomonic skeletal abnormalities including metaphyseal widening and dysostosis. The hematological features of SDS vary, but typically, severe intermittent neutropenia is the initial finding. It is inherited in an autosomal recessive fashion, with germline mutations in the SDS gene accounting for about 95% of patients. Management is multidisciplinary in approach based on the affected organ systems.14
Accident and Emergency
Published in Nagi Giumma Barakat, Get Through, 2006
The most common pancreatic exocrine insufficiency disorder is cystic fibrosis (CF), followed by Shwachman-Diamond syndrome, and, very rarely, trypsinogen, enterokinase, lipase, combined lipase-colipase and pancreatic amylase enzyme deficiencies. Manifestations of Shwachman-Diamond syndrome include short stature, metaphyseal dysplasia, cup-shaped ribs, hypo-splasia of the iliac bones, susceptibility to infection, anaemia with 80% HbF, thrombocytopenia, pancreatic exocrine abnormalities, myelodysplastic syndrome in 33%, skin disorders (eczema and ichthyosis), hepatic dysfunction and cardiac failure. It may present with Hirschprung’s disease, diabetes melli-tus and hepatosplenomegaly. Humoral immunodeficiency is common. Fat loss decreases with age because of the increase in lipase secretion. Learning difficulties are reported in 25% of patients. A sweat test to exclude CF must be performed, and faecal fat studies is important, as well as a pancreatic stimulation test to measure levels of trypsin, amylase and lipase. Bone surveys should be performed to identify skeletal abnormalities not found in any other pancreatic exocrine insufficiency disorders. HbF is found in 80% of patients, and IgA and IgM are low, with low thymine. A white cell function test should be performed to locate the defect in neutrophils. Bone marrow aspiration should be performed to determine whether the patient suffers from myelodysplastic syndrome. Enzyme replacement is important, and can be lifelong.
Ribosomopathies and cancer: pharmacological implications
Published in Expert Review of Clinical Pharmacology, 2022
Gazmend Temaj, Sarmistha Saha, Shpend Dragusha, Valon Ejupi, Brigitta Buttari, Elisabetta Profumo, Lule Beqa, Luciano Saso
4) Shwachman Diamond Syndrome (SDS) is an autosomal recessive disease that generally manifests as bone marrow failure, skeletal deformities, and hypoplasia of the exocrine pancreas [238–240]. SBDS and GTPase elongation factor-like 1 (EFL1) directly catalyze eIF6 removal in mammalian cells via a mechanism that requires GTP binding and hydrolysis by EFL1. The SBDS protein is known to stimulate 60S dependent GTP hydrolysis by elongation factor-like 1 (EFL1), which determines the conformational change of EFL1 and eIF6 (eukaryotic initiation factor 6) removal. The dissociation of eIF6 facilitates the binding of both 40S and 60S ribosomal subunits and 80S maturation [60]. Loss of SBDS expression leads to storage of eIF6 on the late pre-60S subunit and alteration of 80S ribosome assembly [241,242].
Clinical and Mutation Description of the First Iranian Cohort of Infantile Inflammatory Bowel Disease: The Iranian Primary Immunodeficiency Registry (IPIDR)
Published in Immunological Investigations, 2021
Farzaneh Rahmani, Elham Rayzan, Mohammad Reza Rahmani, Sepideh Shahkarami, Samaneh Zoghi, Arezoo Rezaei, Zahra Aryan, Mehri Najafi, Meino Rohlfs, Tim Jeske, Majid Aflatoonian, Zahra Chavoshzadeh, Fatemeh Farahmand, Farzaneh Motamed, Pejman Rohani, Hossein Alimadadi, Alireza Mahdaviani, Mahboubeh Mansouri, Marzieh Tavakol, Mirjam Vanderberg, Daniel Kotlarz, Christoph Klein, Nima Rezaei
We also reported a novel homozygous mutation in the SRP54 gene in patient P10, which was present in homozygous form in his parents and older sibling. Heterozygous mutations in SRP54 have been described in four patients with autosomal dominant form of SCN associated with Shwachman-Diamond syndrome (SDS) phenotype (Bellanne-Chantelot et al. 2018; Carapito et al. 2017), but never in EO-IBD. The SRP54 gene encodes a component of the signal recognition particle (SRP), a ribonucleoprotein responsible for co-translational recognition of secretory molecules and targeting them for the endoplasmic reticulum (ER) (Pool et al. 2002). Dysfunctional SRP leads to ER stress, autophagy and hence P53-dependent apoptosis of promyelocytes in bone marrow of SDS patients, culminating in severe neutropenia (Bellanne-Chantelot et al. 2018). Interestingly, duodenal inflammatory atrophy is seen in up to 50% of patients with SDS and one patient with SDS has been reported with comorbid CD in the literature (Nissen et al. 2019). We speculate that the numeral defect in neutrophils can hinder formation of normal gut barrier against colonic microbiota and predispose patients with SRP54 mutation to IBD, similar to the effect of functional defects in CGD. Nonetheless, preliminary results from our Polyphen and SIFT phenotype prediction algorithms predict the patients p.12 S > L substitution as being benign or tolerated, adding to confusion on the pathophysiology of IBD in this patient. The significance of the homozygous mutation in SRP54 in our patient, and the heterozygous form in his parents and mildly affected sibling, and its association to IBD pathology is pending to be validated through functional studies by our group.
Chronic neutropenia: how best to assess severity and approach management?
Published in Expert Review of Hematology, 2021
Jean Donadieu, Stephanie Frenz, Lauren Merz, Flore Sicre De Fontbrune, Gioacchino Andrea Rotulo, Blandine Beaupain, Martin Biosse-Duplan, Marie Audrain, Laure Croisille, Phil Ancliff, Christoph Klein, Christine Bellanné-Chantelot
Chronic neutropenia, regardless of its cause, but especially congenital neutropenia, predisposes the patient to oral lesions, including aphthous ulcers, gingivitis, periodontitis, and enamel disorders (particularly in Shwachman diamond syndrome). Each person with chronic neutropenia has their own oral disease profile, but all are frail, sometimes with major deterioration in quality of life. Basic care that is easy and affordable is recommended, but a large number of situations require specialized periodontal follow-up. Regular and meticulous tooth brushing should be done twice a day with fluoride toothpaste. Dental follow-up is essential, in addition to follow-up by the referring doctor, and should be regular (2 to 4 times a year depending on the oral condition). It concerns children and adults and may be implemented as soon as the first teeth appear. It is important to preserve the deciduous dentition, to allow normal masticatrory function and harmonious eruption of the permanent teeth. Regular periodontal care including scaling is recommended The use of dental implants is not recommended due to the high risk of jaw bone infections, but exceptions can be made after discussion and collegial decision. In regards to dental braces and orthodontic treatments, they are generally very poorly supported and not recommended. The frequency of periodontitis and resulting tooth loss, which is observed in most of the types of congenital neutropenia, is close to that found for other phagocyte disorders [79], such as leukocyte adhesion deficiency (LAD) [80] and Papillon–Lefevre syndrome (PLS) [81]. These observations suggest interest in a therapeutic approach mediating inflammation, such as cathepsin inhibitors [82] for PLS or interleukin-12 or −23 blockade for LAD [83].