The sulfated polysaccharide dermatan sulfate (DS) forms proteoglycans with a number of distinct core proteins. Iduronic acid-containing domains in DS have a key role in mediating the functions of DS proteoglycans. Two tissue-specific DS epimerases, encoded by DSE and DSEL, and a GalNAc-4-O-sulfotransferase encoded by CHST14 are necessary for the formation of these domains. CHST14 mutations were previously identified for patients with the musculocontractural type of Ehlers-Danlos syndrome (MCEDS). We now identified a homozygous DSE missense mutation (c.803C>T, p.S268L) by the positional candidate approach in a male child with MCEDS, who was born to consanguineous parents. Heterologous expression of mutant full-length and soluble recombinant DSE proteins showed a loss of activity towards partially desulfated DS. Patient-derived fibroblasts also showed a significant reduction in epimerase activity. The amount of DS disaccharides was markedly decreased in the conditioned medium and the cell fraction from cultured fibroblasts of the patient when compared with a healthy control subject, whereas no apparent difference was observed in the chondroitin sulfate (CS) chains from the conditioned media. However, the total amount of CS disaccharides in the cell fraction from the patient was increased ∼1.5-fold, indicating an increased synthesis or a reduced conversion of CS chains in the cell fraction. Stable transfection of patient fibroblasts with a DSE expression vector increased the amount of secreted DS disaccharides. DSE deficiency represents a specific defect of DS biosynthesis. We demonstrate locus heterogeneity in MCEDS and provide evidence for the importance of DS in human development and extracellular matrix maintenance.

BackgroundHepatic dysfunction during pregnancy places both the mother and the fetus at risk. Investigations which are efficient, cost effective and easily available for prognostication are required to tackle this global problem. We studied the etiologies and evaluated investigations for predictive efficiency.MethodsOne hundred ninety-seven pregnant women with hepatic dysfunction during pregnancy were identified. All patients were followed up till 8 weeks after termination of pregnancy or death. Clinico-demographic, biochemical and hematological data were collected and analyzed.ResultsOne hundred ninety-seven of 6,122 females had abnormal liver function tests. Pre-eclampsia (57%), eclampsia (19%), HELLP syndrome (8%), viral infection (6%), hyperemesis gravidarum (5%), intrahepatic cholestasis of pregnancy (4%), chronic liver disease (1%) and sepsis were encountered. There were 41 fetal deaths, 42% preterm deliveries, and NICU admission rate was 27%. Five maternal deaths occurred. Maternal anemia, thrombocytopenia, hyperbilirubinemia and coagulopathy were statistically significant in adverse fetal outcomes. Serum bilirubin performed better than INR as a predictor of both maternal and fetal outcomes.ConclusionsHepatic dysfunction during pregnancy is associated with adverse events for both the mother and the fetus and hypertensive disorders remain the major cause. Maternal bilirubin levels and INR have a role in predicting adverse feto-maternal outcome.

Autosomal recessive congenital ichthyoses are a heterogeneous group of rare cornification diseases. Genetic mutations are responsible for the condition, with some causing a relatively milder phenotype such as ‘self-improving collodion ichthyosis’. In most cases, affected babies are born with a thick parchment like membrane covering their body. These babies may have a problematic postnatal course, and are prone to complications. The authors present the report of a newborn collodion baby afflicted with ALOX12B mutation, who had a challenging post natal course. Difficulties in feeding, temperature control, hydration and electrolyte balance were encountered and required precise monitoring and formulation of an effective treatment strategy. Treatment of jaundice in the baby also presented a unique challenge, which was successfully managed.