Severe congenital neutropenia due to G6PC3 deficiency: Case series of five patients and literature review.

Natalia Velez‐Tirado,Patricia Baeza Capetillo,Marco Antonio Yamazaki‐Nakashimada,Edgar Alejandro Medina Torres,Genny M Chaia Semerena,Kaan Boztug,Jesús Aguirre Hernández,Armando Partida‐Gaytan,Marcos Alejandro Suárez Gutiérrez,Saul O Lugo Reyes,Aristóteles Alvarez‐Cardona,Wojciech Garncarz,Enrique Lopez Valentín,Tatjana Hirschmugl,Sara Elva Espinosa‐Padilla,Christoph Klein,Selma C Scheffler‐Mendoza

doi:10.1111/sji.13136

Abstract

Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency is characterized by severe congenital neutropenia with recurrent pyogenic infections, a prominent superficial venous pattern and cardiovascular and urogenital malformations caused by an alteration of glucose homeostasis, with increased endoplasmic reticulum stress and cell apoptosis. We reviewed our patients with G6PC3 deficiency diagnosed along the last decade in Mexico; we also searched the PubMed/Medline database for the terms ('G6PC3 deficiency' OR 'Dursun syndrome' OR 'Severe congenital neutropenia type 4'), and selected articles published in English from 2009 to 2020. We found 89 patients reported from at least 14 countries in 4 continents. We describe five new cases from Mexico. Of the 94 patients, 56% are male, 48% from Middle East countries and none of them had adverse reactions to live vaccines; all presented with at least 1 severe infection prior to age 2. Seventy-five per cent had syndromic features, mainly atrial septal defect in 55% and prominent superficial veins in 62%. With a total of 94 patients reported in the past decade, we delineate the most frequent laboratory and genetic features, their treatment and outcomes, and to expand the knowledge of syndromic and non-syndromic phenotypes in these patients.

Highlights

While rare diseases are individually infrequent, collectively they afflict around ten percent of the world population
We searched the PubMed/Medline database for the terms (“Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency” OR “Dursun syndrome” OR “Severe congenital neutropenia type 4”), and selected articles published in English from 2009 to 2020
A little over 100 G6PC3 deficiency cases have been described in the literature

Summary

Introduction

While rare diseases are individually infrequent, collectively they afflict around ten percent of the world population. A 3-month-old female patient, born to non-consanguineous Mexican parents, with a family history of three paternal uncles who died before the age of 5 years She first presented with neonatal sepsis requiring intravenous antibiotics, after which she had 5 episodes of pneumonia and a surgically corrected rectovaginal fistula. A 2-year-old female, born to non-consanguineous Mexican parents, was referred to our care for a history of cow’s milk allergy, allergic asthma and rhinitis, recurrent otitis media, sepsis, urinary tract infection, autoimmune colitis and disseminated herpes zoster. On physical examination, she did not have any syndromic features. The patient is alive under treatment with filgrastim (G-CSF) and prophylaxis with TMP-SMZ and fluconazole

Ethics approval

Review of the literature

Discussion

CODE AVAILABILITY

Findings

ETHICS APPROVAL