Causes of prolonged jaundice in infancy: 3-year experience in a tertiary paediatric centre.

UNLABELLED: Although prolonged jaundice (PJ) commonly occurs in infancy, there is not yet agreement as to the appropriate extent of investigations, particularly in otherwise well children. Significant pathologies may present with PJ in this age group and need to be considered. AIM: The aim of this retrospective study was to ascertain the causes of PJ in infants referred to a single tertiary paediatric centre. METHODS: Infants referred with PJ over a 3-year period were identified. Clinical documentation, electronic notes and results of investigations performed prior to and after referral were reviewed. RESULTS: One hundred and sixty-seven infants with PJ were seen. Fifty-eight percent were over 28 days of age. Four patients had conjugated hyperbilirubinaemia. Eighteen percent of patients were found to have a specific medical diagnosis causing or contributing to PJ, almost half of whom had normal clinical examination. The single most common pathological cause for PJ was hypothyroidism found in six patients. CONCLUSIONS: This study demonstrates that normal clinical examination and exclusion of conjugated hyperbilirubinaemia are insufficient to exclude pathological causes of PJ. Overall, these children were referred late. Guidelines, in conjunction with education initiatives, are required to optimise the management of prolonged jaundice in infancy.

Radionuclide cholescintigraphy in genetically confirmed Rotor syndrome.

A 7-year-old girl had been followed up for persistent conjugated hyperbilirubinemia since birth. Alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase activity was within the normal range, and liver protein synthesis had always been normal. Infectious etiology of jaundice, autoimmune diseases, drug-induced liver injury, hemolytic anemia, α-1 anti-trypsin deficiency, Wilson disease and Gilbert syndrome were ruled out. At the age of 8 years the patient underwent radionuclide dynamic cholescintigraphy, indicating poor accumulation of the radiotracer in the liver on one hand, and severe retention of the radiopharmaceutical in the blood pool (including the heart) on the other hand. Rotor syndrome was suspected and finally confirmed on molecular analysis. This case represents the first cholescintigraphy report in a pediatric patient with genetically proven Rotor syndrome.

A child with rotor syndrome and Capillaria philippinensis: case report and review of literature.

This paper reported Capillaria philippinensis in an Egyptian child based on clinical and laboratory diagnosis. The patient was successfullly treated with albendazole.

Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase.

We recently found a markedly lower prevalence of vascular complications, including kidney disease, in diabetic patients with Gilbert syndrome, a congenital form of hyperbilirubinemia, suggesting a beneficial effect of bilirubin (BIL) on diabetic nephropathy. To directly examine this, we determined whether hereditary hyperbilirubinemic Gunn j/j rats and biliverdin (BVD)-treated diabetic db/db mice were resistant to the development of renal disease. Both rodent models had less albuminuria and complete protection against the progression of mesangial expansion accompanied by normalization of transforming growth factor-ß1 and fibronectin expression. Simultaneously, there was normalization of urinary and renal oxidative stress markers, and the expression of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase subunits in the kidney. In cultured vascular endothelial and mesangial cells, BIL and BVD significantly inhibited NADPH-dependent superoxide production, and both high glucose- and angiotensin II-induced production of reactive oxygen species. Collectively, our findings suggest that BIL and BVD may protect against diabetic nephropathy and may lead to novel antioxidant therapies for diabetic nephropathy.

Hiperbilirrubinemia indirecta de origen genético: informe de un caso de síndrome de Crigler-Najjar de tipo II / Indirect hyperbilirubinemia of genetic origin: case report of Crigler-Najjar syndrome type II

El síndrome de Crigler Najjar II aparece por un déficit en la conjugación de la bilirrubina debido a la deficiencia parcial de la enzima uridindifosfato-glucuronil transferasa. Por lo general, tiene un curso benigno, a diferencia del Crigler Najjar de tipo I, donde el déficit enzimático es total y los afectados mueren a edades tempranas. Se presenta el caso de una adolescente de16 años con hiperbilirrubinemia indirecta, síndrome convulsivante y parálisis cerebral. Una correcta historia clínica con estudio genealógico y pruebas funcionales apropiadas, permitieron determinar el diagnóstico definitivo. Esta enfermedad genética se transmite de forma autosómica recesiva, tiene una prevalencia muy baja a nivel mundial y constituye, en general, un reto diagnóstico para los médico.

Crigler Najjar syndrome type II is related to a defect of bilirubin conjugation due to partial deficiency of the enzyme uridine diphosphate-glucuronyl transferase. Usually has a benign course, unlike Crigler Najjar type I, where the enzyme deficiencyis total and the affected patients usually die at early ages. We present the case of a teenager with indirect hyperbilirubinemia, seizures and cerebral palsy. A good clinical historywith pedigree and appropriate functional tests allowed us to determine the definitive diagnosis. This is an autosomal recessive disorder, has a very low prevalence worldwide, and is adiagnostic challenge for physicians in general.

Hiperbilirrubinemia indirecta de origen genético: informe de un caso de síndrome de Crigler-Najjar de tipo II / Indirect hyperbilirubinemia of genetic origin: case report of Crigler-Najjar syndrome type II

El síndrome de Crigler Najjar II aparece por un déficit en la conjugación de la bilirrubina debido a la deficiencia parcial de la enzima uridindifosfato-glucuronil transferasa. Por lo general, tiene un curso benigno, a diferencia del Crigler Najjar de tipo I, donde el déficit enzimático es total y los afectados mueren a edades tempranas. Se presenta el caso de una adolescente de16 años con hiperbilirrubinemia indirecta, síndrome convulsivante y parálisis cerebral. Una correcta historia clínica con estudio genealógico y pruebas funcionales apropiadas, permitieron determinar el diagnóstico definitivo. Esta enfermedad genética se transmite de forma autosómica recesiva, tiene una prevalencia muy baja a nivel mundial y constituye, en general, un reto diagnóstico para los médico.(AU)

Crigler Najjar syndrome type II is related to a defect of bilirubin conjugation due to partial deficiency of the enzyme uridine diphosphate-glucuronyl transferase. Usually has a benign course, unlike Crigler Najjar type I, where the enzyme deficiencyis total and the affected patients usually die at early ages. We present the case of a teenager with indirect hyperbilirubinemia, seizures and cerebral palsy. A good clinical historywith pedigree and appropriate functional tests allowed us to determine the definitive diagnosis. This is an autosomal recessive disorder, has a very low prevalence worldwide, and is adiagnostic challenge for physicians in general.(AU)

Hereditary spherocytosis coexisting with Gilbert's syndrome: a diagnostic dilemma.

Haemolytic anaemia generally gives rise to only a modest elevation of serum bilirubin. Unconjugated hyperbilirubinaemia of an extreme degree should raise suspicion of additional factors, such as Gilbert's syndrome, hepatocellular dysfunction or renal failure. We present a 17-year-old boy with hereditary spherocytosis coexisting with Gilbert's syndrome.

Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism.

Homozygous HbE [beta26(B8)Glu-->Lys] is a clinically mild disorder with no significant symptoms. However, we have frequently noted hyperbilirubinemia among patients with homozygous HbE in the Indian population, with jaundice being the major complaint at presentation. A study of the UGT1A1 gene polymorphism shows that the variant TA7 in the promoter region of the UGT1A1 gene is associated with hyperbilirubinemia in homozygous HbE patients.

Safety of paclitaxel in a patient with ovarian cancer and hyperbilirubinemia due to Rotor's syndrome.

BACKGROUND: Rotor's syndrome is a rare congenital disorder characterized by functional hyperbilirubinemia. Treatment decision may be challenging in a cancer patient with Rotor's syndrome, since the majority of the antineoplastic agents are metabolized in the liver and excreted via the biliary system. We report the first case of paclitaxel administration in a patient with ovarian cancer and elevated bilirubin levels due to Rotor's syndrome. CASE: A 50-year-old woman with Rotor's syndrome had an exploratory laparotomy and was diagnosed to have stage IIIC epithelial ovarian cancer. The baseline serum bilirubin value was 15.3 mg/dL. She was started on a 50% dose of 87.5 mg/m(2) paclitaxel by 3-h infusion plus carboplatin AUC-6. The paclitaxel dose was increased by 25% at consecutive cycles until the standard dose of 175 mg/m(2)/3 h was achieved. Six cycles were administered without any metabolic derangement. The patient was rendered disease free with this treatment. CONCLUSION: Paclitaxel appears to be safe to administer to cancer patients with functional hyperbilirubinemia.

Lithocholate-3-O-glucuronide-induced cholestasis. A study with congenital hyperbilirubinemic rats and effects of ursodeoxycholate conjugates.

The mechanism of lithocholate-3-O-glucuronide-induced cholestasis is unknown. In this study, we investigated the cholestatic effects of this agent in a congenital hyperbilirubinemic rat, EHBR. We also studied the effects of ursodeoxycholate-3-O-glucuronide and tauroursodeoxycholate on lithocholate-3-O-glucuronide-induced cholestasis in rats. Lithocholate-3-O-glucuronide, administered at the rate of 0.1 mumol/min/100 g for 40 min, a cholestatic dose in control rats, failed to cause cholestasis in EHBR, and biliary lithocholate-3-O-glucuronide excretion was delayed. Biliary concentrations of this agent did not correlate with the severity of cholestasis. Both tauroursodeoxycholate and ursodeoxycholate-3-O-glucuronide, infused at the rate of 0.2 mumol/min/100 g for 120 min, completely inhibited cholestasis induced by lithocholate-3-O-glucuronide administered at the rate of 0.1 mumol/min/100 g for 40 min. Only tauroursodeoxycholate enhanced biliary lithocholate-3-O-glucuronide excretion. These findings indicate that lithocholate-3-O-glucuronide-induced cholestasis is induced by damage at the level of the bile canalicular membrane. Ursodeoxycholate-3-O-glucuronide inhibits this cholestasis, possibly by inhibiting the access of lithocholate-3-O-glucuronide to the bile canalicular membrane.

Phosphofructokinase deficiency (Tarui disease) associated with hepatic glucuronyltransferase deficiency (Gilbert's syndrome): a case and family study.

Tarui disease is a rare, genetically determined glycogen storage myopathy caused by the total lack of phosphofructokinase (PFK) enzymatic activity in the muscles and partially deficient enzymatic activity in the erythrocytes. We describe a patient with this disorder, who presented with exercise intolerance, painful cramps, elevation of muscle enzyme levels in the serum, compensated hemolysis with paradoxically elevated hemoglobin levels and gout with overproduction of uric acid. This patient had a partial hepatic uridine diphosphoglucuronate-glucuronyltransferase deficiency (Gilbert's syndrome). The coexistence of these two enzymatic deficiencies resulted in a complex clinical picture, especially during and after muscular effort. Screening of the patient's family revealed asymptomatic PFK deficiency in the erythrocytes of both parents and sister.

[A case of possible lovastatin-induced pancreatitis in concomitant Gilbert syndrome]. / Ein Fall möglicher Lovastatin-induzierter Pankreatitis bei gleichzeitigem Gilbert-Syndrom.

A patient is described in whom treatment with the cholesterol-lowering agent Lovastatin (Mevacor MSD) led to a slight to moderate elevation of amylase and bilirubin with the occurrence of symptoms attributable to mild pancreatitis. These symptoms were sufficiently severe to require discontinuation of the drug. The concomitant existence of Gilbert's syndrome in this patient may have been causally related to the non-tolerance of this valuable drug. Although a penetrating ulcer cannot be ruled out in the differential diagnosis, the overall evidence favours the diagnosis of Lovastatin pancreatitis, a so far unpublished complication.

Haem biosynthesis in the unconjugated hyperbilirubinaemias: observations in the Gunn rat model.

Disturbances of the enzymes of haem biosynthesis have been reported in patients with unconjugated hyperbilirubinaemia. We have examined the excretion of haem precursors in the Gunn rat which suffers from severe unconjugated hyperbilirubinaemia. In urine, levels of aminolaevulinic acid and total porphyrin were significantly reduced when compared to controls. In feces both coproporphyrin and protoporphyrin levels were reduced in Gunn rats, the former being more affected. Blood porphyrin levels in control and Gunn rats were similar.

Síndrome de Rotor: apresentaçäo de um caso

Os autores apresentam um caso de síndrome de Rotor em paciente de 65 anos que desde os 10 anos apresenta icterícia assintomática, por hiperbilirrubinemia conjugada. A presença de colecistite calculosa e a operaçäo realizada mostraram a perfeita integridade do fígado e ductos biliares