Antiviral treatment in congenital HCMV infection: The six-year experience of a single neonatal center in Poland.

BACKGROUND: Antiviral treatment is recommended for symptomatic newborns with congenital cytomegalovirus infection (cCMV). OBJECTIVES: To compare 2 treatment methods in neonates with cCMV - ganciclovir-based therapy (intravenous ganciclovir (GCV) or sequential GCV + valganciclovir (VGCV) therapy) with oral VGCV-based therapy - in Polish neonates. MATERIAL AND METHODS: A total of 98 symptomatic infants with cCMV (positive HCMV DNA in urine ≤21st day of life) hospitalized in the neonatal intensive care unit (NICU) between 2012 and 2017 were enrolled. Clinical characteristics, the viral load in blood and urine, hematological and biochemical tests, neuroimaging results, and the length of hospitalization were compared between the study groups at baseline and at the 2nd hospitalization. RESULTS: In 2012, GCV was used in 57% of the cases, sequential therapy in 33% and VGCV in 10%. In 2017, VGCV monotherapy was used in 83% of the infants treated. Valganciclovir treatment allowed the length of hospitalization to be shortened over 2.5 times during the six-year observation period. Infants treated intravenously had lower birth weights and head circumferences, and more frequently presented splenomegaly, petechiae, thrombocytopenia, and hepatitis. The baseline viral load in the blood and urine were similar in both groups, but at follow-up visits 4-6 weeks later, a viral load about 70 times lower was observed in the blood of the VGCV-based group (1029 viral copies/mL compared to 72,188 viral copies/mL in the GCV-based group; p = 0.04). The prevalence of neutropenia was similar in both groups at the follow-up visits. CONCLUSIONS: Valganciclovir became the first line of antiviral therapy in cCMV in the study population. Compared to GCV-based therapy, VGCV monotherapy allowed shorter hospital stays and reduced the viral load in blood due to continuing treatment at home. Valganciclovir monotherapy did not provoke more side effects such as neutropenia. Intravenous GCV is still suitable for patients with severe disseminated disease, born prematurely, with low birth weights, or not tolerating enteral feeding. In those infants, the sequential therapy seems to be optimal.

A case of severe trichothiodystrophy 3 in a neonate due to mutation in the GTF2H5 gene: Clinical report.

Trichothiodystrophy (TTD) is a group of predominantly autosomal recessive disorders characterized by sulfur-deficient brittle hair. Clinical features of TTD consist of variable neuroectodermal symptoms including ichthyosis, nail abnormalities, mental retardation, short stature, decreased fertility and proneness to infections. Approximately half of the reported patients with TTD have clinical and cellular photosensitivity associated with mutations in three subunits (ERCC3, ERCC2, GTF2H5) of the basal transcription factor TFHII, which is involved in transcription and nucleotide excision repair. We report on a case of a male neonate with a novel GTF2H5 gene mutation, detected by whole exome sequencing. The GTF2H5 gene's role is to provide stability to the entire TFHII complex. The reported patient was born at 33 weeks' gestation from a pregnancy complicated by intrauterine growth restriction and premature rupture of membranes. His main clinical problems included severe congenital ichthyosis and proneness to infections with episodes of multiorgan failure. The infant's history displays the most severe clinical manifestations among patients with GTF2H5 gene mutations that have so far been reported.