RESUMEN
Osteogenesis imperfecta (OI) is an inherited disorder with osteoporosis and recurrent fractures. Children presenting with recurrent fractures and bowing of limbs have severe form of the disorder. Patients carrying homozygous WNT1 mutations have more frequent fractures while heterozygous carriers of the mutation in WNT1 gene are also found to have early onset osteoporosis. We identified a family with novel WNT1 mutation. The index case, a 6 month old child presented with fractures from early infancy. Next generation sequencing (NGS)done for the child didn't show any variations in other OI genes including COL1A1, COL1A2, SERPINH1, CRTAP, LEPRE1, PP1B, 1F1TM5 and BMP1 genes. Sanger sequencing showed 41bp deletion in splice region following exon 1 of WNT1 gene in homozygous state. The mutation was found to be likely pathogenic on bioinformatic analysis. To further characterize the significance of the mutation we studied his mother who is 30 year old with blue sclera and history of backache but no fractures. Her DXA scan of lumber spine showed osteoporosis and she was heterozygous for the mutation. The child's DXA scan showed T-score of -6.4â¯at lumbar spine level. Father also has history of backache and was carrier for the same deletion variant. The child was given 3 doses of zoledronate and did not have any further fractures. Thus, we conclude that this novel variant identified in the child with OI is likely cause for the disease and possibly zoledronate has a role in prevention of fractures in this case.
Asunto(s)
Fracturas Óseas/genética , Osteogénesis Imperfecta/genética , Proteína Wnt1/genética , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Variación Genética , Humanos , Imidazoles/uso terapéutico , Lactante , Masculino , Mutación , Osteogénesis Imperfecta/tratamiento farmacológico , Ácido ZoledrónicoRESUMEN
OBJECTIVE: To evaluate the effect of fluconazole prophylaxis on invasive fungal infection (IFI) in very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU). METHODS: VLBW infants receiving antibiotics for more than 3 days were randomized to receive either fluconazole (6 mg/kg) or placebo, every other day for 7 days followed by everyday till day 28 or discharge whichever was earlier. The primary outcome was IFI, and secondary outcome was fungal attributable mortality and all-cause mortality. RESULTS: The incidence of IFI was significantly lower (21%) in the fluconazole group compared to the control group (43.2%, 95%CI 0.09-0.37, p < 0.05). The ARR (absolute risk reduction) was 22.2% and the NNT (number needed to treat) was 5. Fungal attributable mortality was also lower in the fluconazole group (2.6% versus 18.9%, 95%CI 0.003-0.52, p < 0.05). CONCLUSION: In VLBW neonates on the NICU, use of fluconazole prophylaxis decreases IFI and fungal attributable mortality.