title: Intracranial hemorrhage as the initial manifestation of a congenital disorder of glycosylation.
abstract: Intracranial hemorrhage in a term neonate is a rare event in the absence of an identifiable precipitating factor such as severe thrombocytopenia, mechanical trauma, asphyxia, infections, or congenital vascular malformations. Congenital disorders of glycosylation are a genetically and clinically heterogeneous group of multisystem disorders characterized by the abnormal glycosylation of a number of glycoproteins. Although bleeding caused by abnormal glycosylation of various coagulation factors is a well-known clinical complication of several types of congenital disorders of glycosylation, intracranial hemorrhage has not been reported as an initial manifestation of this entity. Here we report the detailed history of a family with 2 consecutive male infants, both born at term with intracranial hemorrhage diagnosed within the first 24 hours of life. The diagnosis of a congenital disorder of glycosylation was established in the second infant by an abnormal glycosylation of serum transferrin detected by electrospray-ionization mass spectrometry. Both infants showed significant neurologic deterioration during the first month of life, and both died at 5 months of age. Intracranial hemorrhage in a term neonate without a potential precipitating factor represents yet another clinical feature that should raise the suspicion for a congenital disorder of glycosylation.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Children's Center, Johns Hopkins University School of Medicine, 600 N Wolfe St, Blalock 1008, Baltimore, Maryland 21205, USA. rcohn2@jhmi.edu
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Cohn
authors.forename: Erik
authors.initials: E
authors.lastname: Eklund
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Bergner
authors.forename: James F
authors.initials: JF
authors.lastname: Casella
authors.forename: S Lee
authors.initials: SL
authors.lastname: Woods
authors.forename: Janyne
authors.initials: J
authors.lastname: Althaus
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Blakemore
authors.forename: Harold E
authors.initials: HE
authors.lastname: Fox
authors.forename: Julie E
authors.initials: JE
authors.lastname: Hoover-Fong
authors.forename: Ada
authors.initials: A
authors.lastname: Hamosh
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Braverman
authors.forename: Hudson H
authors.initials: HH
authors.lastname: Freeze
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
mesh_terms: D001049:Apnea / Q000209:etiology; D001921:Brain / Q000473:pathology; D002239:Carbohydrate Metabolism, Inborn Errors / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D002543:Cerebral Hemorrhage / Q000151:congenital* / Q000209:etiology; D002769:Cholelithiasis / Q000209:etiology; D003025:Clubfoot; D003286:Contracture / Q000151:congenital; D017809:Fatal Outcome; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006408:Hematoma, Subdural / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009122:Muscle Hypertonia / Q000209:etiology; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012131:Respiratory Insufficiency / Q000209:etiology; D021241:Spectrometry, Mass, Electrospray Ionization; D014168:Transferrin / Q000737:chemistry; D000979:alpha-2-Antiplasmin / Q000172:deficiency
chemical_list: D006023:Glycoproteins; D014168:Transferrin; D000979:alpha-2-Antiplasmin