Acetaminophen administration in a patient with Gilbert's syndrome.

The patient was an 8-year-old Japanese girl with Gilbert's syndrome (GS). Based on the DNA analysis, she was homozygous for a T-to-G transversion at nucleotide position 1456 in the UGT1A1 gene, leading to the substitution of aspartate for tyrosine at position 486 of the UGT1A1 enzyme. Because this mutation is located in an exon common to UGT1A genes, all the UGT1A enzymes may be affected. It is well-known that UGT1A1, UGT1A6 and UGT1A9 enzymes glucuronidate acetaminophen. To evaluate acetaminophen tolerance in the patient, serum acetaminophen levels were determined after oral administration of acetaminophen (15 mg/kg). The maximum serum acetaminophen level reached (12.8 µg/mL) was far below the toxic level. The finding suggested that the usual therapeutic dose of acetaminophen is safe for the GS patient. The combination of mutation analysis in UGT1A1 and acetaminophen loading test may be useful to avoid adverse effect in GS patients.

Treatment of preterm infants with West syndrome: differences due to etiology.

BACKGROUND: This study was conducted with a particular focus on preterm infants with West syndrome (WS) to evaluate differences in the first responses to oral medication based on etiology. METHODS: Medical records of 53 patients with WS, treated at five institutions between 2005 and 2009, were reviewed retrospectively. Patients were divided into six groups based on the time of brain insult, and evaluated for short-term outcomes using oral anti-epileptic agents and synthetic adrenocorticotropic hormone. RESULTS: The sample consisted of 15, six, 14, two, four, and 12 patients classified, on the basis of apparent time of acquisition of etiology, into the prenatal, term, preterm, postnatal, other, and no identified etiology groups, respectively. Average age of onset in the term group was 3.3 ± 1.0 months, significantly earlier than in the prenatal, preterm, postnatal and no identified etiology groups (P < 0.05). All patients in the term group had experienced seizures before the onset of WS. Only patients in the preterm group had only experienced neonatal seizures, and responded better to treatment. Patients in the preterm group had better responses to treatment, especially oral medication, compared with those in the prenatal and term groups. The prevalence of relapse of seizures in the preterm group (14%) was significantly lower than that in the prenatal group. CONCLUSIONS: Preterm WS patients responded well to treatment. Distinguishing WS patients on the basis of different etiologies is important for evaluating the effectiveness of treatment.

A homozygous mutation in UGT1A1 exon 5 may be responsible for persistent hyperbilirubinemia in a Japanese girl with Gilbert's syndrome.

The UGT1A1 gene encodes a responsible enzyme, UDP-glucuronosyltransferase1A1, for bilirubin metabolism. Many mutations have already been identified in patients with inherited disorders with hyperbilirubinemia, Crigler-Najjar syndrome and Gilbert's syndrome. In this study, we identified a UGT1A1 mutation in an 8-year-old Japanese girl with persistent hyperbilirubinemia who was clinically diagnosed as having Gilbert's syndrome. For the mutational analysis of UGT1A1, we performed a full sequence analysis of the gene using the patient's DNA. She was homozygous for a T to G transversion at nucleotide position 1456 in UGT1A1 exon 5 (c.1456T>G), leading to the substitution of aspartate for tyrosine at position 486 of the UGT1A1 protein (p.Y486D). In conclusion, the homozygous mutation of UGT1A1 may be responsible for persistent hyperbilirubinemia in this patient.