Clinical decision limits for interpretation of direct bilirubin--a CALIPER study of healthy multiethnic children and case report reviews.

OBJECTIVE: Measurement of total and direct bilirubin is routinely performed for the differential diagnosis of hyperbilirubinemias. The diagnostic efficiency of a test is dependent on the chosen clinical decision limit. This study is designed to address the clinical decision limits for direct bilirubin. DESIGN AND METHODS: Routine laboratory method was used to measure total and direct bilirubin in children up to the age of 18years. Case study data and serum from a group of healthy children were analyzed and statistical exercise was performed to establish decision limits. RESULTS: The reference interval for total bilirubin was 1-12µmol/L and for direct bilirubin 1-9µmol/L with the median direct bilirubin of 3µmol/L. In 17% of children with non-pathological jaundice, median total bilirubin was 173µmol/L, median direct bilirubin was 8µmol/L and median direct bilirubin percent was 49%. From birth direct bilirubin percentage decreased until total bilirubin was 41µmol/L, then it remained at ≤10%. Albumin increased with age, and was on average 2.4g/L higher when measured using bromocresol-green compared with bromocresol-purple. An increased amount of direct bilirubin was observed when albumin (detected using the bromocresol-purple method) was >35g/L. CONCLUSIONS: Direct bilirubin concentration of ≥10µmol/L should be used to consider the presence of conjugated hyperbilirubinemia provided that total bilirubin is also above the reference interval. A high direct bilirubin percentage is unlikely to offer any clinical value when total bilirubin is not increased. It is, however, a useful diagnostic tool when there is a persistence of hyperbilirubinemia or when total bilirubin increases during times of stress with direct bilirubin >10%.

Novel mutations in the Dubin-Johnson syndrome gene ABCC2/MRP2 and associated biochemical changes.

A patient with sepsis and jaundice was admitted for diagnosis and treatment. Associated biochemical changes included increased C-reactive protein, conjugated bilirubin and gamma-glutamyltransferase, the duration of which was protracted. High urine coproporphyrin isomer-1 and immunostaining of liver tissue suggested Dubin-Johnson syndrome. DNA sequencing using polymerase chain reaction amplification of the ABCC2 gene revealed the patient to have a compound heterozygous variant of MRP2, a molecule involved in canalicular transport of bilirubin. There was a history of jaundice since infancy.

Serum calcium, urine calcium and polymorphisms of the calcium sensing receptor gene.

BACKGROUND: Recent studies have suggested a correlation between the A986S polymorphism of the calcium sensing receptor (CASR), and serum total and ionized calcium. This study aimed to assess the prevalence of three CASR polymorphisms in a West of Scotland population and relate genotype to serum and urine calcium levels. METHODS: Fasting blood and urine samples were obtained from 121 healthy male and female volunteers aged 20-60 years. Volunteers were genotyped for the A986S, Q1011E and R990G polymorphisms using allele-specific amplification and amplification-created restriction site techniques. Total calcium, ionized calcium and urine calcium excretion were measured using automated clinical chemistry analysers. RESULTS: Genotype frequencies for the A986S polymorphism were: AA, 74.4%; AS, 24.8%; SS, 0.8%. There was a small but statistically significant (P < 0.01) increase in ionized calcium concentration in AS individuals compared with the wild type (1.22 versus 1.20 mmol/L). No statistical difference was detected in serum total calcium or parameters of urine calcium excretion. Genotype frequencies for the remaining polymorphisms were: RR, 82.6%; RG, 16.5%; GG, 0.8% and QQ, 93.4%; QE, 6.6%; EE, 0%. Biochemical parameters in these individuals were not statistically different from the wild type. CONCLUSION: The increase in serum ionized calcium in the AS group was small and, therefore, unlikely to be of clinical significance.

Hyperamylasaemia and multiple myeloma.

This case report describes a 42-year-old Caucasian woman who presented with persistent hyperamylasaemia and no evidence of pancreatic pathology. Further investigations resulted in a diagnosis of light-chain multiple myeloma. Amylase production by epithelial tumours has been well documented but the association with multiple myeloma has only been described in a small number of cases. The link does not appear to be immunoglobulin class-specific but the association with Bence Jones myeloma is unusual. The common features in this group of patients have been extensive extramedullary spread with a high tumour mass and a poor prognosis. This case was similar in that the patient showed very rapid disease activity developing extensive metastatic lesions and treatment ultimately proved unsuccessful. The amylase concentrations have been shown to decrease in response to treatment and increase at times of relapse and it has been proposed that it may be useful as a tumour marker in these patients. This case study adds to the pool of patents with this unusual association.