Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: report of five new cases and review.

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

In vitro inactivation of pulmonary surfactant replacement preparations by serum albumin.

Inactivation of the surface activity of pulmonary surfactant by serum proteins is an important part of neonatal respiratory distress syndrome. The ability of serum proteins to diminish the surface activity of surfactant preparations used to treat respiratory distress syndrome has not been fully described. The sensitivity of clinically useful pulmonary replacement preparations beractant (Survanta) and colfosceril palmitate, cetyl alcohol, and tyloxapol (Exosurf) to albumin inactivation was examined in vitro by the Wilhelmy plate technique. At a final lipid concentration of 0.1 mg/mL and in the absence of albumin, both Survanta and Exosurf exhibited equilibrium surface tensions in the range of 35 dynes/cm. In the presence of albumin, range of 35 dynes/cm. In the presence of albumin, the surface tension of Survanta was markedly higher. Maximal response of Survanta to albumin was observed at about 1 mg/mL protein concentration. When the lipid concentration was raised to 0.3 mg/mL, the presence of albumin had little effect. With Exosurf, the presence of albumin resulted in only minor elevations of surface tension, even at an albumin concentration 10-fold greater than that used in the experiments with Survanta. These results indicate that at lipid concentrations of 0.1 mg/mL and less, the surface activity of the bovine purified lung surfactant Survanta is more sensitive to the presence of albumin than is the synthetic preparation Exosurf.

Surfactant disposition in rats with monocrotaline-induced pneumotoxicity.

Monocrotaline (MCT)-treated rats exhibit airways and gas exchange abnormalities which precede development of sustained pulmonary hypertension (Lai et al., 1991). Because the density of type II pneumocytes is reduced in MCT-treated rat lungs (Wilson and Segall, 1990), decreased abundance or activity of type II pneumocyte-derived surfactant may contribute to pulmonary dysfunction. On the other hand, since the remaining type II pneumocytes undergo an apparent hypertrophic response, it is possible that they compensate for the reduction in population density by elaborating more surfactant or surfactant with enhanced surface activity. As an initial means of discriminating between these possibilities, the amount, surface activity, and synthesis rate of surfactant was examined in rats at 1, 2, and 3 weeks after MCT administration. The amounts of surfactant phospholipid and protein recovered in bronchoalveolar lavage fluid did not differ substantially between control and MCT-treated rats at any time post MCT administration. Similarly, neither the initial rate of surface tension reduction nor the maximum reduction in surface tension differed between surfactant preparations recovered from control and MCT-treated rats. The rate of surfactant synthesis in lung explants, as determined by incorporation of [3H]glycerol into phospholipid, also was not different between MCT-treated and control rats at any time after MCT administration. MCT treatment failed to alter the distribution of [3H]glycerol into surfactant phospholipid. Collectively, these data indicate that airways abnormalities in MCT-treated rats cannot be ascribed to a reduction in the abundance or the activity of surfactant. Furthermore, in light of previous studies indicating that the density of type II pneumocytes is reduced in MCT pneumotoxicity, the present findings suggest that surfactant regulatory pathways must undergo a compensatory response that preserves normal functional status.