The Smith-Lemli-Opitz syndrome (SLOS) is caused by deficient ⌬ 7 -dehydrocholesterol reductase, which catalyzes the final step of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursors 7-dehydrocholesterol (7DHC) and 8DHC. We hypothesized that i ) 7DHC and 8DHC accumulation contributes to the poor outcome of SLOS patients and ii ) blood exchange transfusions with hydroxymethylglutaryl (HMG)-CoA reductase inhibition would improve the precursor-to-cholesterol ratio and may improve the clinical outcome of SLO patients. First, an in vitro study was performed to study sterol exchange between plasma and erythrocyte membranes. Second, several exchange transfusions were carried out in vivo in two SLOS patients. Third, simvastatin was given for 23 and 14 months to two patients. The in vitro results illustrated rapid sterol exchange between plasma and erythrocyte membranes. The effect of exchange transfusion was impressive and prompt but the effect on plasma sterol levels lasted only for 3 days. In contrast, simvastatin treatment for several months demonstrated a lasting improvement of the precursor-to-cholesterol ratio in plasma, erythrocyte membranes, and cerebrospinal fluid (CSF). Plasma precursor concentrations decreased to 28 and 33% of the initial level, respectively, whereas the cholesterol concentration normalized by a more than twofold increase. During the follow-up period all morphometric parameters improved. The therapy was well tolerated and no unwanted clinical side effects occurred. This is the first study in which the blood cholesterol level in SLOS patients is normalized with a simultaneous significant decrease in precursor levels. There was a lasting biochemical improvement with encouraging clinical improvement. Statin therapy is a promising novel approach in SLOS that deserves further studies in larger series of patients.
Pulmonary hypertension is well documented prior to extra corporeal membrane oxygenation and response very quickly to the institution of treatment. Ultra sound techniques are indicated at the bedside, and prove useful in monitoring pulmonary blood pressure during the procedure.
Renal failure in the newborn infant is mainly determined by vascular causes. In this report we describe a patient with a particular vascular cause of renal failure. The patient was the product of a twin pregnancy in which the twin partner died in utero. In retrospect, the twins appeared to be monozygotic. As the pregnancy was studied carefully prenatally by ultrasound, we were able to observe the development of this condition, characterized by oliguria, oligohydramnios, and lung hypoplasia: the oligohydramnios sequence. After organ development had been normal initially, renal function was lost and the oligohydramnios sequence developed in the survivor after the co-twin had died in utero.
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