An Earlier, Moore Severe Presentation of G6PC3 Deficiency in a Male Infant From Mexico

Background . Severe congenital neutropenia is a bone marrow failure syndrome characterized by severe neutropenia present from birth. We present a case of G6PC3 deficiency presenting at an earlier age, with a more severe clinical picture than previously reported.

Case report. A 3-month-old boy, born to nonconsanguineous parents was delivered by C-section at 35 weeks gestation. He was admitted to neonatal intensive care unit for prematurity and poor respiratory effort requiring mechanical ventilation. Aggressive antimicrobial therapy was started for nosocomial pneumonia and severe persistent neutropenia. Physical examination: Poor weight, chest accessory venous vasculature, parasternal systolic murmur grade I left, testicles not palpable in scrotal sac.  Laboratory workup> Total leukocyte blood count with 2400mm³, total neutrophils 200mm³. Echocardiogram revealed pulmonary hypertension: 58mmHg, foramen ovale with bidirectional shunt. Abdominal ultrasound: kidneys with hydronephrosis grade I in the right kidney and grade III left, confirmed by Excretory urography. Esophago-gastroduodenal Series: velopalatal incompetence, pyloric hypertrophy, spontaneous gastroesophageal reflux and upper third of the esophagus. Hearing screening reported bilateral hearing loss. Nissen fundoplication, Stamm gastrostomy and pyloromyotomy was performed. Treatment with Recombinant human G-CSF was started (3-5mgKd) with good response. Mutational analysis revealed a single-nucleotide deletion in exon 2, which results in a frameshift and premature stop codon, predicting a nonfunctional trunk protein.

Conclusion.  Severe congenital neutropenia type 4 is an autosomal recessive condition, which was defined recently with identification of the causative mutations in G6PC3 and is characterized by congenital neutropenia and variable developmental disorders: cardiovascular (atrial septal defects, pulmonary hypertension) and/or urogenital system (urachal fistulations and cryptorchidism).  Some patients show a peculiar visibility of subcutaneous veins. Patients with G6PC3 deficiency lack mature neutrophils in the bone marrow and have increased susceptibility to apoptosis in peripheral neutrophils. Recombinant human G-CSF is the first-line therapy.  This is only the second case identified in Latin America, and the first one in Mexico.  Compared to what has been previously reported, however, our patient presented earlier and with a more severe clinical picture, including bilateral hydronephrosis.  Stem-cell transplantation has never been performed in G6PC3 deficiency, but it´s being considered in this case given the patient young age and severity.