Novel G6PC3 Mutations in patients with Congenital Neutropenia: Case reports and Review of the Literature

2021 ◽  
Vol 21 ◽  
Author(s):  
Seyed Farzad Maroufi ◽  
Zoha Shaka ◽  
Helia Mojtabavi ◽  
Mona Sadeghalvad ◽  
Elham Rayzan ◽  
...  
Keyword(s):  
Heart Defects ◽  
Case Reports ◽  
Severe Neutropenia ◽  
Prior History ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
First Case ◽  
History Of

Background: Severe congenital neutropenia (SCN4) caused by mutations in glucose-6-phosphatase catalytic subunit 3 (G6PC3) is characterized by recurrent infections due to severe neutropenia, and it may be accompanied by other extra-hematopoietic manifestations; including structural heart defects, urogenital abnormalities, prominent superficial venous markings, growth retention, and inflammatory bowel diseases with rare incidence. The homozygous or compound heterozygous mutations of G6PC3 are responsible for most cases of autosomal recessive SCN4. Herein, we present two cases of SCN4 affected by novel mutations in the G6PC3, in addition to a summarized list of variants in G6PC3 gene that are reported as pathogenic and related to the SCN4 phenotype. Case presentation: Herein we present two cases of SCN4; the first case was a three-months old boy with severe neutropenia and prior history of hospitalization due to umbilical separation, umbilical herniation, omphalitis, and pyelonephritis; and the second case was an eight-year-old with a history of neutropenia, recurrent and severe episodes of intractable diarrhea, refractory rectovaginal and rectoperineal fistula, congenital inguinal hernia, and ASD type 2. Whole exome sequencing was performed for both cases and revealed two novel homozygous missense mutations in G6PC3 that were predicted to be deleterious; c.337G>A, p. Gly113Arg in the first case and c.479C>T; P. Ser160Leu in the second case. To our knowledge, both of these two mutations has not been reported in the G6PDC3 gene. Conclusions: In patients with severe neutropenia with varying extra hematopoietic syndrome, mutation of G6PC3 should be suspected after ruling out other mutations related to neutropenia. This study pointed toward novel G6PC3 mutations, that should be considered in order to diagnose patients with severe congenital neutropenia.

scholarly journals Kostmann Syndrome With Neurological Abnormalities: A Case Report and Literature Review

2020 ◽  
Vol 8 ◽  
Author(s):  
Baiyu Lyu ◽  
Wei Lyu ◽  
Xiaoying Zhang
Keyword(s):  
Gene Mutations ◽  
Severe Neutropenia ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Hematopoietic Stem ◽  
Case Presentation ◽  
Neurological Abnormalities ◽  
Kostmann Syndrome ◽  
History Of

Background: Severe congenital neutropenia (SCN), also known as Kostmann syndrome, is a rare heterogeneous group of diseases characterized by arrested neutrophil maturation in the bone marrow.Case Presentation: We report a case of Kostmann syndrome and review previously reported SCN cases with neurological abnormalities. A 10-year-old boy had a history of recurrent, once a month, infection starting at 6 months of age. He had neutropenia for more than 9 years, as well as intellectual disability. He was homozygous for the exon 3 c.430dupG mutation of the HAX1 gene NM-006118. After treatment of antibiotics and G-CSF, his symtoms were relieved and was 3 months free of infection. The search revealed 29 articles related to Kostmann syndrome caused by HAX1 gene mutation; they were screened, and the main clinical features of 13 cases of Kostmann syndrome with neurological abnormalities were summarized and analyzed.Conclusions: Kostmann syndrome has three main characteristics: severe neutropenia (<0.2 × 109/L), maturation arrest of granulopoiesis at the promyelocyte stage, and death due to infections. HAX1 gene mutations affecting both isoforms A and B are associated with additional neurological symptoms. G-CSF can improve and maintain neutrophil counts, and improve prognosis and quality of life. At present, hematopoietic stem cell transplantation is the only cure.

Antineutrophil Antibodies Lead to Mistaken Identity in Severe Congenital Neutropenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 385-385 ◽  
Author(s):  
Laurence A. Boxer ◽  
Audrey Anna Bolyard ◽  
Beate Schwinzer ◽  
Darryl Glaser ◽  
Kenneth Dougan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Otitis Media ◽  
Bone Marrow Examination ◽  
Myelogenous Leukemia ◽  
Positive Test ◽  
Severe Neutropenia ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Benign Condition ◽  
History Of

Abstract Autoimmune Neutropenia of Infancy (ANI) is generally regarded as a benign condition diagnosed by finding neutropenia and a positive test for antineutrophil antibodies. To determine whether the presence of antineutrophil antibodies in infancy always predicts a benign disease, data were reviewed for young children with positive antineutrophil tests who are enrolled in the Severe Chronic Neutropenia International Registry (SCNIR). A set of identical twins presented with severe neutropenia at age 5 months. Twin A1 had a preceding history of aphthous ulcers, cellulitis, recurrent otitis media, pneumonitis, an episode of bacteremia and a positive test for antineutrophil antibodies<INS cite=mailto:%20 dateTime=2005-08-01T10:53>.</INS> Twin A2 had a preceding history of cellulitis, otitis media, and pneumonitis. The median absolute neutrophil count (ANC) of twin A1 and twin A2 was 0.280 x 109/L and 0.116 x 109/L, respectfully and bone marrow examination for twin A1 showed maturation arrest at the myelocyte-metamyelocyte level. With the diagnosis of ANI in one twin, both twins were placed on granulocyte-colony stimulating factor (G-CSF), because of frequent fever and recurrent infections. Fifty-one months after the diagnosis of immune neutropenia, twin A1 developed acute myelogenous leukemia. Further studies then revealed that both twins had a mutation in the neutrophil elastase gene (ELA2) at exon 5 resulting in a nucleotide substitution from TGC to TGA, which indicated a diagnosis of severe congenital neutropenia. Another set of fraternal twins were identified to have ANI at six months because of recurrent abscesses, mouth ulcers, otitis media and positive tests for antineutrophil antibodies. The ANC was 0.067 x 109/L in twin B1 and 0.166 x 109/L in twin B2. At age 31 months twin B1 developed a severe Clostridial infection, which led to the loss of his right leg and part of the anterior abdominal wall. Subsequently both twins were placed on G-CSF. Prior to G-CSF treatment, bone marrow studies revealed an arrest at the promyelocyte stage and an ELA2 mutation in exon 4 leading to a TCG to TTG substitution in both twins thereby indicating a diagnosis of severe congenital neutropenia. Upon further review of the SCNIR, eight other congenital patients were identified to have antineutrophil antibodies and bone marrow patterns consistent with severe congenital neutropenia. In conclusion, it is important to be aware that positive antineutrophil antibodies can occur associated with severe congenital neutropenia. Infants with severe neutropenia and repeated or severe bacterial infections should have a bone marrow examination and ELA2 evaluation to establish correctly the underlying pathogenesis of the neutropenia.

scholarly journals Clozapine-induced stuttering in the absence of known risk factors: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Florence Jaguga
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Side Effect ◽  
Case Reports ◽  
Extrapyramidal Symptoms ◽  
Prior History ◽  
Case Presentation ◽  
Rare Side Effect ◽  
History Of ◽  
Electrophysiological Findings

Abstract Background Stuttering is a rare side effect of clozapine. It has been shown to occur in the presence of one or more factors such as abnormal electrophysiological findings and seizures, extrapyramidal symptoms, brain pathology, and a family history of stuttering. Few case reports have documented the occurrence of clozapine-induced stuttering in the absence of these risk factors. Case presentation A 29-year-old African male on clozapine for treatment-resistant schizophrenia presented with stuttering at a dosage of 400 mg/day that resolved with dose reduction. Electroencephalogram findings were normal, and there was no clinical evidence of seizures. The patient had no prior history or family history of stuttering, had a normal neurological examination, and showed no signs of extrapyramidal symptoms. Conclusion Clinicians ought to be aware of stuttering as a side effect of clozapine, even in the absence of known risk factors. Further research should investigate the pathophysiology of clozapine-induced stuttering.

scholarly journals Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Tham Thi Tran ◽  
Quang Van Vu ◽  
Taizo Wada ◽  
Akihiro Yachie ◽  
Huong Le Thi Minh ◽  
...  
Keyword(s):  
Early Onset ◽  
Bacterial Infections ◽  
Complete Blood Count ◽  
Hereditary Diseases ◽  
Severe Neutropenia ◽  
Sequencing Analysis ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Direct Dna Sequencing ◽  
Life Threatening

Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.

Abstract WP190: Clinical Features of Sarcoid Patients With Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Ahmed Z Obeidat ◽  
Heidi Sucharew ◽  
Charles J Moomaw ◽  
Dawn O Kleindorfer ◽  
Brett M Kissela ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Current Knowledge ◽  
Case Reports ◽  
Brain Mri ◽  
Sporadic Case ◽  
Prior History ◽  
Stroke Patients ◽  
Stroke Subtype ◽  
Stroke Event ◽  
History Of

Background: Current knowledge on ischemic stroke in sarcoid patients stems from sporadic case reports. The mechanism is thought to be related to granulomatous involvement of brain vasculature. However, clinical, demographic, and radiographic features of sarcoid patients with ischemic stroke are lacking. If sarcoid patients are at higher risk for ischemic stroke event, we hypothesized that the risk factors for ischemic stroke and stroke subtype distribution would differ between sarcoid and non-sarcoid ischemic stroke patients. Methods: Cases of ischemic stroke were identified for the years 2005 and 2010 from the population-based Greater Cincinnati/Northern Kentucky Stroke Study (population 1.3 million). Ischemic stroke cases were physician study confirmed and patients with a history of sarcoid were identified through medical chart review. Clinical variables were compared between stroke patients with history of sarcoid and those with no prior sarcoid history. Results: A total of 4258 cases of ischemic stroke were identified; of them, only 18 had prior diagnosis of sarcoid (0.04%). Brain MRI showed diffusion restriction in 14 out of 15 (93%) MRIs performed in sarcoid patients. The table presents risk factor and subtype data on sarcoid patients compared with non-sarcoid patients. Conclusions: We identified only a few cases of prior sarcoid history in our two-year ascertainment of ischemic stroke patients in our population. In comparison with stroke patients with no prior history of sarcoid, the sarcoid patients tended to be of younger age at presentation, female, have a history of diabetes and hyperlipidemia, and more likely of African descent, perhaps related to the diagnosis of sarcoid itself. We were unable to detect differences in stroke subtype distributions between sarcoid and non-sarcoid ischemic stroke patients.

scholarly journals Subsequent Development of Desmoid Tumor after a Resected Gastrointestinal Stromal Tumor

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Areen Abdulelah Murshid ◽  
Hatim Q. Al-Maghraby
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Desmoid Tumor ◽  
Case Reports ◽  
Previous History ◽  
Subsequent Development ◽  
Stromal Tumor ◽  
Desmoid Tumors ◽  
Mesenchymal Tumors ◽  
First Case ◽  
History Of

Desmoid tumors (deep fibromatosis) of the mesentery are rare mesenchymal tumors. They are often misdiagnosed, especially with a previous history of resection for gastrointestinal stromal tumor (GIST). Immunohistochemistry can help differentiate between these two tumors. In this article, we present a case we had encountered: a Desmoid tumor developing in a patient with a history of GIST 3 years ago. It is the first case of GIST with subsequent development of Desmoid tumor to be reported in Saudi Arabia. We discuss the two entities of Desmoid tumor and GIST by comparing their definitions, clinical presentations, histological features, immunohistochemistry stains, molecular pathogenesis, prognosis, and treatment. We also discuss the relationship between GIST and the subsequent development of Desmoid tumors and compare our case with case reports in literature.

scholarly journals Metastatic Pancreatic Cancer with BRAF and P53 Mutations: Case Report of Therapeutic Response to Doublet Targeted Therapy

2020 ◽  
Vol 13 (3) ◽  
pp. 1239-1243
Author(s):  
Shenthol Sasankan ◽  
Lorraine Rebuck ◽  
Gloria Darrah ◽  
Moises Harari Turquie ◽  
Ian Rabinowitz
Keyword(s):  
Pancreatic Cancer ◽  
Case Report ◽  
Targeted Therapy ◽  
Therapeutic Response ◽  
Case Reports ◽  
Clinical History ◽  
P53 Mutation ◽  
Metastatic Pancreatic Cancer ◽  
First Case ◽  
History Of

We report on the clinical history of a 49-year-old female with metastatic pancreatic cancer. She was initially treated with standard chemotherapy as per current guidelines. She was found to have both a BRAF and P53 mutation, and received dabrafenib and trametinib with deep responses, both radiographically and biochemically (CA19-9). Her response has been more clinically relevant than responses in previous case reports of patients with BRAF-positive pancreatic cancer treated with targeted therapy. To the best of our knowledge, this is the first case report showing a dramatic therapeutic response to combination therapy with dabrafenib and trametinib in metastatic pancreatic cancer.

scholarly journals A UNIQUE CASE OF ATEZOLIZUMAB-INDUCED AUTOIMMUNE DIABETES

2020 ◽  
Vol 6 (1) ◽  
pp. e30-e32
Author(s):  
Mimi Wong ◽  
Nirjhar Nandi ◽  
Ashim Sinha
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Autoimmune Diabetes ◽  
Case Reports ◽  
Zinc Transporter ◽  
Prior History ◽  
Unique Case ◽  
Cell Lung Carcinoma ◽  
Zinc Transporter 8 ◽  
First Case

Objective: Immunotherapy is a novel treatment that can cause autoimmune diabetes in rare cases. More cases occur following use of the inhibitor to the protein programmed cell death-1 rather than the inhibitor to programmed cell death-ligand 1. Methods: We report a unique case of autoimmune diabetes following atezolizumab use. Results: A 55-year-old, Aboriginal Australian female with no prior history of diabetes was commenced on atezolizumab for recurrent squamous cell lung carcinoma. Two months following its commencement, there was the onset of fatigue, polyuria, polydipsia, and new hyperglycemia. Subsequently she was found to have a borderline-low C peptide level of 0.6 nmol/L (reference range is 0.5 to 1.0 nmol/L), and positive zinc transporter-8 antibodies. Following the diagnosis of autoimmune diabetes, 5 units of glargine insulin was commenced which maintained euglycemia and resolved her symptoms of hyperglycemia. Conclusion: There are few case reports of atezolizumab-induced autoimmune diabetes. We present the first case associated with zinc transporter-8 antibodies, and a unique case of autoimmune diabetes in a patient of Aboriginal Australian background.

Agranulocytosis Associated with Waldenström Macroglobulinemia

2018 ◽  
Vol 140 (1) ◽  
pp. 42-45 ◽  
Author(s):  
Iuliana Vaxman ◽  
Daniel Shepshelovich ◽  
Lucille Hayman ◽  
Pia Raanani ◽  
Meir Lahav
Keyword(s):  
Case Report ◽  
Febrile Neutropenia ◽  
Medical History ◽  
Case Reports ◽  
Neutropenic Fever ◽  
Severe Neutropenia ◽  
Past Medical History ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
History Of

Currently, there are only 2 case reports of Waldenström macroglobulinemia (WM) associated with severe neutropenia. This is a case report of a woman with a past medical history of WM who presented with neutropenic fever. The patient’s febrile neutropenia resolved after RCD chemotherapy (cyclophosphamide 750 mg/m2, dexamethasone 20 mg, and rituximab 375 mg/m2). Fourteen days after administration, the neutrophil level had started to rise and normalized after 6 days. To the best of our knowledge, this is the 3rd reported case of agranulocytosis due to WM.

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