Diagnosis and treatment of a 16-year-old Chinese patient with concurrent hereditary hemochromatosis and Gilbert's syndrome.

Gilbert's syndrome and hereditary hemochromatosis predominantly affect Caucasians with a low incidence in Asians. Here we report the case of a 16-year-old Chinese boy, who was admitted with hepatalgia, jaundice, hyperpigmentation, and splenomegaly to our hospital. After excluding chronic hepatitis, autoimmune disorders, and alcohol or drug injury, genetic analyses of the patient and his parents revealed simultaneous manifestations of Gilbert's syndrome and hereditary hemochromatosis, though his parents did not develop related symptoms. The presented case indicates that diagnoses of Gilbert's syndrome and hereditary hemochromatosis should be taken into consideration when chronic hepatitis is suspected without a clear etiology.

Hereditary hyperbilirubinemias.

Inherited disorders of bilirubin metabolism involve four autosomal recessive syndromes: Gilbert, CriglerNajjar, Dubin-Johnson and Rotor, among which the first two are characterized by unconjugated and the second two by conjugated hyperbilirubinemia. Gilbert syndrome occurs in 2%-10% of general population, while others are rare. Except for Crigler-Najjar syndrome, hereditary hyperbilirubinemias belong to benign disorders and thus no treatment is required.

Crigler-Najjar syndrome type I in a Turkish newborn caused by a novel mutation and Gilbert type genetic defect.

Crigler-Najjar syndrome (CNS), caused by deficiency of bilirubin uridine diphosphate glucuronosyltransferase (UGT) 1A1, is a rare and autosomal recessive inherited disorder characterized by severe unconjugated nonhemolytic hyperbilirubinemia since birth. We present a girl with CNS type I caused by a novel mutation and Gilbert type genetic defect. Gilbert's Syndrome (GS) and CNS type I both involve abnormalities in bilirubin conjugation secondary to deficiency of bilirubin UGT. The combined defects even in benign genetic forms were shown to cause more serious clinical disease. The patient has been treated with daily home-based phototherapy for more than nine months and considered as a candidate for liver transplantation.

[Gilbert syndrome]. / Gilbert-szindróma.

Gilbert disease is a benign disorder of the bilirubin conjugation, which affects 7-10% of the average population. The symptoms are usually only mild jaundice and the slightly elevated unconjugated bilirubin level, other laboratory tests and the liver functions are usually normal. In most cases, mutation of the UDP glucuronyltransferase gene leads to impaired bilirubin conjugation. Besides the usual laboratory methods, genetic analyses of the UDP glucuronyltransferase gene can help in the diagnosis. In 80-100% of the patients the (TA)-insertion in the promoter-region of the gene is present in homozygous - (TA) 7 /(TA) 7 - form, and leads to the decrease of the amount of functionally active enzyme. The role of missense mutations localized in the coding region has not been clarified yet, but their co-occurrence with the (TA) 7 promoter-variant might mean an explanation to the elevated bilirubin level, jaundice, and the familiar aggregation of Gilbert disease.

[Main symptom jaundice--differential diagnosis at the bedside]. / Ikterus--Differentialdiagnose am Krankenbett.

In jaundice, tissues are yellow in color because of an excessive deposition of bilirubin secondary to hyperbilirubinemia. Bilirubin is the physiological end-product of heme metabolism. Jaundice is one of the main symptoms of hepatobiliary disease. Besides that, it might occur in the setting of cardiac, hematologic or pancreatic disorders. The onset of jaundice varies from acute with severe impairment of general condition to chronic and not being noticed by the patient at all. In the first part of this review, the physiological and pathophysiological molecular mechanisms of heme and bile metabolism are described in detail on a scientific basis. The knowledge of the main principles of heme degradation, canalicular bile secretion and enterohepatic cycling of bile salts helps to understand, why clinicians differentiate between prehepatic (hemolytic), hepatocellular and obstructive jaundice. A detailed patient's history and a careful physical examination are essential for the clinical differential diagnosis of jaundice. In combination with routinely obtained lab results, it is often possible to find the right diagnosis already at the bedside. To demonstrate this, the second part of this review sets the focus on the analysis of three case reports from the clinical point of view. The differential diagnosis of jaundice is summarized in a table.

Concomitant Gilbert's syndrome and thalassemia trait.

A 23 years old male presented with fluctuating jaundice since age of five years. He was diagnosed to have thalassemia trait along with Gilbert's syndrome. He had disproportionately higher bilirubin concentration for either disorder alone. The importance of the concomitance of these disorders is highlighted.

Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias.

Congenital familial non-haemolytic hyperbilirubinaemias are potentially lethal syndromes caused by genetic lesions that reduce or abolish hepatic bilirubin UDP-glucuronosyltransferase activity. Here we describe genetic defects that occur in the UGT1 gene complex that cause three non-haemolytic unconjugated hyperbilirubinaemia syndromes. The most severe syndrome, termed Crigler-Najjar syndrome type I, is mainly associated with mutations in exons 2 to 5 that affect all UGT1 enzymes and many of the mutations result in termination codons and frameshifts. Crigler-Najjar type II syndrome which is treatable with phenobarbital therapy is associated with less dramatic missense mutations or heterozygous expression of mutant and normal alleles. Gilbert's syndrome, the most prevalent (2-19% in population studies) and mildest of the three syndromes is principally caused by a TA insertion at the TATA promoter region upstream of the UGT1A1 exon. Current methods used for the diagnosis and treatment of these diseases are discussed.

Gilbert syndrome.

Two or three times a year, a healthy patient (> 1 year old) with mild unconjugated hyperbilirubinemia as the only abnormality on routine liver function testing will be referred to the gastroenterologist. A diagnosis of Gilbert Syndrome (GS) is made, and the patient may or may not be seen in the clinic or office because GS is a benign condition. Either way, the nurse needs to understand the pathophysiology of this condition so he/she can provide necessary patient/family education. The purpose of this article is to review the existing literature on GS and to summarize it in a manner useful to both nurses and families.