Central diabetes insipidus: A rare complication of IVH in a very low birth weight preterm infant.

A 710 g male infant was born at a referring hospital at a gestational age of 23 weeks and 2 days via vaginal delivery and was transferred to our facility at 14 days of age. His delivery was complicated by the breech presentation with difficult head extraction. The infant's initial course was significant for respiratory distress syndrome, grade III-IV intraventricular hemorrhage (IVH), acute kidney injury, and large PDA. On the day of life 29, a gradual increase in serum sodium level refractory to increasing total fluid volume was noted. The combination of persistent hypernatremia (150-160 mmol/l), polyuria (8.4 ml/kg/hr), high plasma osmolality (323 mosm/kg), hyposthenuria (75 mosm/kg) and an undetectable serum ADH (<0.8 pg/ml) confirmed the diagnosis of central diabetes insipidus (CDI). Serum sodium and urine output decreased and urine osmolality increased after subcutaneous DDAVP administration.CDI is an uncommon cause of hypernatremia in the neonatal period. The diagnosis can be difficult as excessive urine output and high serum sodium can often be attributed to high insensible water loss in the extremely premature newborn. CDI in our patient was thought to be due to grade III-IV IVH complicated by post-hemorrhagic hydrocephalus.In conclusion, the diagnosis of central DI should be considered as a complication of severe IVH in the extremely premature neonate who demonstrates persistent hypernatremia, polyuria, decreased urine osmolality, and increased plasma osmolality. Serum ADH levels can be helpful in confirming the central origin of DI and subcutaneous desmopressin can be an effective treatment in the preterm infant.

Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation.

Hereditary surfactant protein B (SP-B) deficiency has been lethal in the first year of life without lung transplantation. We tested the hypothesis that SP-B gene mutations may result in milder phenotypes by investigating the mechanisms for lung disease in two children with less severe symptoms than have been previously observed in SP-B deficiency. Immunostaining patterns for pulmonary surfactant proteins were consistent with SP-B deficiency in both children. DNA sequence analysis indicated that both children were homozygous for a mutation in exon 5 that created an alternative splice site. Reverse transcriptase PCR and sequence analysis confirmed use of this splice site, which resulted in a frameshift and a premature termination codon in exon 7. The predominant reverse transcriptase PCR product, however, lacked exon 7, which restored the reading frame but would not allow translation of the exons that encode mature SP-B. Western blot analysis detected reduced amounts of mature SP-B as well as an aberrant SP-B proprotein that corresponded to the size expected from translation of the abnormal transcript. We conclude that a novel splicing mutation was the cause of lung disease in these children and that hereditary SP-B deficiency can be the cause of lung disease in older children.