ABSTRACT
Background: Crigler-Najjar syndrome (CN) clinically manifests as intense unconjugated hyperbilirubinemia without evidence of hemolysis. At present, over 90 genetic variations such as mutations, insertions, or deletions have been described in the five exons of the UDP-glucuronosyltransferase (UGT1A1) gene responsible for defect of bilirubin conjugation.Objective: To report a case of a female CN type I child who presented with unconjugated hyperbilirubinemia, normal liver function tests, and normal ultrasonographic images of the liver.Results: Peak total bilirubin in this patient was 27.6 mg/dL. She developed kernicterus despite prolonged daily home phototherapy. Exons 1-5 of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the UGT1A1 gene was screened for mutations by direct DNA sequencing. Molecular genetic analysis showed that this patient was homozygous for a nonsense mutation at nucleotide number 715 (715C→T) in exon 1 resulting in the replacement of glutamine (CAG, amino acid 239) by a stop codon (TAG).Conclusion: Detection of this genetic defect is essential for gene therapy and can be used as a prenatal screening test to identify the affected offspring.
ABSTRACT
Objective: To study prospectively the prevalence, clinical presentations and laboratory findings of enterovirus (EV) infection in infants under 3 months of age who present as a sepsis-like syndrome. Method: All infants less than 3 month of age admitted as a sepsis-like syndrome to King Chulalongkorn Memorial Hospital between April 2003 and February 2004 were included. Patients who were immunocompromised or who had been admitted for longer than 14 days before developing symptoms were excluded. A detailed history, physical and laboratory findings were recorded and analyzed. Specimens of blood and cerebrospinal fluid were tested for enteroviruses using Nucleic Acid Sequence-Based Amplification (NASBA). Patients were followed to determine the clinical outcome and duration of hospitalization. Results: Of 56 infants, thirty-six were admitted to the pediatric wards and 20 had been hospitalized since birth in the neonatal intensive care unit (NICU) or nursery wards. Enterovirus infection was diagnosed in 13 (36.1 %) of the patients admitted to the pediatric wards and none in the group of NICU/nursery patients. The most common clinical presentations were high grade fever (92 %), rashes (77 %) and lethargy (54 %) as compared to fever (78.3 %), poor feeding (60.9 %) and lethargy (56.5 %) in the EV negative group. Ten (76.9 %) of the enterovirus positive infants had evidence of central nervous system (CNS) involvement as evidenced by the presence of EV RNA in cerebrospinal fluid (CSF) or CSF pleocytosis plus EV RNA in blood and/or CSF. Nevertheless, CSF pleocytosis was found in only 7 infants (53.8 %). Average duration of illness was 3.2 days as compared to 3.5 days in the nonenteroviral group with similar clinical features. All enterovirus positive patients had an uncomplicated recovery. Ten (76.9 %) received parenteral antibiotics for a mean of 5 days (versus 4.8 days in enterovirus negative group). The average length of stay was 8.1 days as compared to 15 days in enterovirus negative group. Conclusion: Enterovirus infections are important causes of a sepsis-like syndromes in infants under 3 months of age. Most enterovirus infected patients presented with fever without localizing signs and rashes. Detection of enterovirus RNA by NASBA in serum and/or CSF represents a rapid method for the diagnosis of enterovirus infection in infants presenting with a sepsis-like syndrome. Keywords: Enterovirus, infant, NASBA, sepsis.