iloprost and Abnormalities--Multiple

Transposition of the great arteries (TGA) in the newborn combined with persistent pulmonary hypertension was reported previously to occur in 3-12 % of full-term neonates with TGA. Right-to-left shunting at the ductal level causes severe hypoxemia despite prostaglandin infusion and balloon atrial septostomy. Although the introduction of inhaled nitric oxide (iNO) has improved the prognosis, this condition still is associated with high preoperative mortality. This report describes the case of a newborn with TGA and persistent pulmonary hypertension, which was managed successfully with oral sildenafil, iNO, and inhaled iloprost during life-threatening acute pulmonary hypertension, thus preventing the use of extracorporeal membrane oxygenation.

Topics: Abnormalities, Multiple; Administration, Inhalation; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Iloprost; Infant, Newborn; Male; Persistent Fetal Circulation Syndrome; Pulmonary Wedge Pressure; Transposition of Great Vessels; Vasodilator Agents

Alternatively spliced GNAS1 and XL-GNAS1, encoding respectively the stimulatory G-protein alpha-subunit (Gsalpha) and the extra-large stimulatory G-protein alpha-subunit (XLsalpha), are located on the imprinted chromosomal region 20q13.12-13. We presently report a functional polymorphism in the imprinted XL-GNAS1 gene. In three patients, a 36 bp insertion and two basepair substitutions flanking this insertion were found in the paternally inherited XL-GNAS1 exon 1. They clinically manifest an enhanced trauma-related bleeding tendency and a variable degree of mental retardation. A platelet aggregation inhibition test to evaluate Gs function was developed. Their platelets display Gs hyperfunction and an enhanced cAMP generation upon stimulation of Gs-coupled receptors. The prevalence of the XLsalpha insertion in a normal control group was 2.2%. Normal controls, inheriting the insertion maternally, had a normal platelet Gs activity, whereas controls inheriting the insertion paternally had increased inducible platelet Gs activity, defining the insertion as a functional polymorphism. This paternally inherited XLsalpha insertion represents a new genetic cause of an inherited bleeding tendency, although to a variable degree.

Topics: Abnormalities, Multiple; Adenosine; Adenylyl Cyclases; Adolescent; Alprostadil; Alternative Splicing; Amino Acid Sequence; Amino Acid Substitution; Bleeding Time; Blood Platelets; Child; Chromogranins; Cyclic AMP; Female; Fingers; Gene Frequency; Genomic Imprinting; GTP-Binding Protein alpha Subunits, Gs; Hemorrhagic Disorders; Heterotrimeric GTP-Binding Proteins; Humans; Hyperkinesis; Hypoparathyroidism; Iloprost; Intellectual Disability; Male; Molecular Sequence Data; Muscle Hypotonia; Mutagenesis, Insertional; Nerve Tissue Proteins; Phenotype; Platelet Aggregation; Platelet Function Tests; Polymorphism, Genetic; Protein Subunits; Repetitive Sequences, Amino Acid; Risk Factors; Second Messenger Systems; Structure-Activity Relationship; Wounds and Injuries