A case of early onset life-threatening epilepsy associated with a novel ATP1A3 gene variant

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.

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Expanding Contributions of Monogenic Very Early Onset Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab145 ◽

2021 ◽

Author(s):

Jodie Ouahed

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Early Onset ◽

Current Issue ◽

Epithelial Barrier ◽

Mevalonate Kinase Deficiency ◽

Bowel Diseases ◽

Life Threatening ◽

Mucosal Homeostasis ◽

Inflammatory Bowel

Abstract Currently over 70 genes known to be causative in very early onset inflammatory bowel disease (VEOIBD) have been identified. In the current issue of Inflammatory Bowel Diseases, 2 articles describing monogenetic forms of VEOIBD are highlighted. One describes a patient with life-threatening VEOIBD and a mutation in ITGA6, illustrating the importance of the epithelial barrier in maintaining mucosal homeostasis. The other describes the presentation and management of 10 patients with VEOIBD secondary to damaging mutations in MVK, resulting in mevalonate kinase deficiency. Though most monogenic causes of VEOIBD remain “private,” understanding the different categories of pathways affected in children with VEOIBD is critical and has already resulted in invaluable insight in the management of patients with VEOIBD and may hold strong implications for the care of IBD overall.

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The Use of Plasma Exchange in a Very Early-onset and Life Threatening, Hemolysis, Elevated Liver Enzymes, and Low Platelet (HELLP) Syndrome: A Case Report

Gynecology & Obstetrics ◽

10.4172/2161-0932.1000387 ◽

2016 ◽

Vol 6 (6) ◽

Author(s):

Iannaccone A ◽

Tyczynski B

Keyword(s):

Case Report ◽

Plasma Exchange ◽

Early Onset ◽

Hellp Syndrome ◽

Liver Enzymes ◽

Elevated Liver Enzymes ◽

Life Threatening

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Early-Onset Pneumococcal Sepsis in Newborn Infants

PEDIATRICS ◽

10.1542/peds.60.3.352 ◽

1977 ◽

Vol 60 (3) ◽

pp. 352-355

Author(s):

Robert Bortolussi ◽

Theodore R. Thompson ◽

Patricia Ferrieri

Keyword(s):

Early Onset ◽

Streptococcal Infection ◽

Group B Streptococcus ◽

Newborn Infants ◽

Clinical Signs ◽

Pneumococcal Sepsis ◽

Life Threatening ◽

Group B ◽

Onset Group ◽

Early Onset Group

Five infants with pneumococcal sepsis presented with respiratory distress and clinical signs of infection in the first day of life. Although there was no apparent epidemiological relationship among the patients, four of the five were seen within a 12-month period. Pneumonia, prolonged rupture of fetal membranes, and prematurity were features in these patients. Three infants died, two within 12 hours of diagnosis. Streptococcus pneumoniae was isolated from the vagina of three of the mothers; in two, the serotype was identical to that recovered from their infants. Clinical features of neonatal pneumococcal sepsis are similar to those of early-onset group B streptococcal infection. Like the group B Streptococcus, S. pneumoniae acquired from the maternal vagina is a potential life-threatening pathogen in the newborn period.

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Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219865597 ◽

2019 ◽

Vol 26 (3) ◽

pp. 747-753 ◽

Cited By ~ 2

Author(s):

Dimitra Ioanna Lampropoulou ◽

Konstantinos Laschos ◽

Anna-Lea Amylidi ◽

Ariadni Angelaki ◽

Nikolaos Soupos ◽

...

Keyword(s):

Early Onset ◽

Dehydrogenase Deficiency ◽

Colorectal Cancer Patient ◽

Dihydropyrimidine Dehydrogenase ◽

Efficacy And Safety ◽

Review Of The Literature ◽

Time Restrictions ◽

Timely Access ◽

Life Threatening ◽

Chemotherapy Dose

Fluoropyrimidine-based regimens are among the most commonly used chemotherapy combinations for the treatment of solid tumors. Several genetic polymorphisms that are implicated with fluoropyrimidine anabolism and catabolism have been associated with the development of life-threatening toxicities. Uridine triacetate is an FDA-approved antidote for 5-fluorouracil or capecitabine overdose and early-onset, life-threatening toxicity within 96 h of last chemotherapy dose. To date, it is not accessible for Greek patients as per the current summary of product characteristic's time restrictions. We report and discuss the course and outcome of capecitabine toxicity in a 66-year-old female colorectal cancer patient with heterozygous dihydropyrimidine dehydrogenase deficiency. This paper highlights the difficulty in timely access of this lifesaving medication for Greek and possibly other European patients.

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Clinical and therapeutic features of myasthenia gravis in adults based on age at onset

Neurology ◽

10.1212/wnl.0000000000008903 ◽

2020 ◽

Vol 94 (11) ◽

pp. e1171-e1180 ◽

Cited By ~ 8

Author(s):

Elena Cortés-Vicente ◽

Rodrigo Álvarez-Velasco ◽

Sonia Segovia ◽

Carmen Paradas ◽

Carlos Casasnovas ◽

...

Keyword(s):

Myasthenia Gravis ◽

Early Onset ◽

Late Onset ◽

Age At Onset ◽

Neuromuscular Diseases ◽

Cross Sectional ◽

Life Threatening ◽

Onset Group ◽

Anti Acetylcholine

ObjectiveTo describe the characteristics of patients with very-late-onset myasthenia gravis (MG).MethodsThis observational cross-sectional multicenter study was based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases. Patients were classified into 3 age subgroups: early-onset MG (age at onset <50 years), late-onset MG (onset ≥50 and <65 years), and very-late-onset MG (onset ≥65 years). Demographic, immunologic, clinical, and therapeutic data were reviewed.ResultsA total of 939 patients from 15 hospitals were included: 288 (30.7%) had early-onset MG, 227 (24.2%) late-onset MG, and 424 (45.2%) very-late-onset MG. The mean follow-up was 9.1 years (SD 4.3). Patients with late onset and very late onset were more frequently men (p < 0.0001). Compared to the early-onset and late-onset groups, in the very-late-onset group, the presence of anti–acetylcholine receptor (anti-AChR) antibodies (p < 0.0001) was higher and fewer patients had thymoma (p < 0.0001). Late-onset MG and very-late-onset MG groups more frequently had ocular MG, both at onset (<0.0001) and at maximal worsening (p = 0.001). Although the very-late-onset group presented more life-threatening events (Myasthenia Gravis Foundation of America IVB and V) at onset (p = 0.002), they required fewer drugs (p < 0.0001) and were less frequently drug-refractory (p < 0.0001).ConclusionsPatients with MG are primarily ≥65 years of age with anti-AChR antibodies and no thymoma. Although patients with very-late-onset MG may present life-threatening events at onset, they achieve a good outcome with fewer immunosuppressants when diagnosed and treated properly.

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Characteristics and outcome of early-onset, severe forms of Wiskott-Aldrich syndrome

Blood ◽

10.1182/blood-2012-08-448118 ◽

2013 ◽

Vol 121 (9) ◽

pp. 1510-1516 ◽

Cited By ~ 50

Author(s):

Nizar Mahlaoui ◽

Isabelle Pellier ◽

Cécile Mignot ◽

Jean-Philippe Jais ◽

Chrystèle Bilhou-Nabéra ◽

...

Keyword(s):

Early Onset ◽

Distinct Subgroup ◽

Wiskott Aldrich Syndrome ◽

Key Points ◽

Life Threatening ◽

Matched Donor

Key Points This study identified a distinct subgroup of WAS patients with an early onset (before the age of 2 years) of severe, life-threatening manifestations. HSCT is a curative strategy in this subgroup of patients and should be performed as early in life as possible, even when a fully matched donor is lacking.

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