Outcome of hepatobiliary scanning: preterm versus full-term cholestatic infants.

OBJECTIVES: The aims of this study were to evaluate the specificity of a non-draining hepatobiliary scintigraphy (HBS) for biliary atresia (BA) in preterm and full-term babies, to verify the relationship between non-draining scan and higher levels of direct bilirubin and to find an objective criterion to guide the time in performing HBS. METHODS: A total of 175 infants (113 males and 62 females, median age of 45 days) with 181 HBS performed in Tuen Mun Hospital between January 1998 and May 2010 were retrospectively analysed. A 'non-draining' scan was defined as one showing no excretion of radiolabelled tracer into the small bowel 24 h after injection. The disease category, epidemiological and laboratory data were compared between infants having non-draining and draining scans. In addition, the predictive value of a negative scan for BA was compared between preterm and full-term infants. RESULTS: Twenty infants (11.4%) were surgically confirmed to have BA. A non-draining scan was found to be 100% sensitive for BA, and the specificity was 96% and 78% among full-term infants and preterm infants, respectively. The mean direct bilirubin values of infants with BA and intrahepatic cholestasis were 141.9 and 111.3 µmol/L, respectively, which were significantly higher than 67.2 µmol/L seen in infants with draining scans. This analysis shows that using direct bilirubin ≥63 µmol/L as an objective criterion in guiding the time to perform HBS is most cost-effective. CONCLUSION: Our data supported that using direct bilirubin ≥63 µmol/L as an objective criterion in guiding the time to perform HBS will avoid unnecessary scans.

Electronic chemical pathology consultation service and dried blood spot metabolic screening in hospital patients.

AIM: Inborn errors of metabolism (IEM) are an unpopular and difficult subject and most clinicians are unfamiliar with them. Although chemical pathologists have a long-standing practice in advising test strategy and result interpretation especially from primary care, such consultations are usually informal, unstructured and those related to IEM are infrequently requested. This study aims to provide a formal electronic consultation service and to apply tandem mass spectrometry-based dried blood spot metabolic screening (DBSM) as a rapid first-line test for patients suspected of IEM. METHODS: DBSM and a chemical pathology consultation were ordered through the hospital computer terminals. DBSM detected 29 metabolic disorders. The clinical data and metabolic results for the 12-month period were reviewed. RESULTS: There were 279 consultations of which 209 were initiated by paediatricians and 70 by adult physicians. The main reasons for consultation were developmental delay, neurological abnormalities, unexplained biochemical abnormalities and monitoring of patients with IEM. There were 158 DBSM requests. One positive case of isovaleric acidaemia was detected. CONCLUSIONS: All high-risk paediatric patients should have a DBSM and a timely electronic chemical pathology consultation as a rapid and cost-effective first-line screening. Provision of a visible, accessible and helpful consultation service enables professional reimbursement.

Fatal viral infection-associated encephalopathy in two Chinese boys: a genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variants.

Influenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele [p.Phe352Cys; p.Val368Ile] were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0+C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of [p.Phe352Cys; p.Val368Ile] among Hong Kong Chinese was 0.104, similar to Japanese data, and [p.Phe352Cys] has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE.

A 12-year-old chinese girl with Cushing syndrome and virilization due to adrenocortical carcinoma.

A Chinese adolescent girl presented with secondary amenorrhea. During follow-up, she gradually developed Cushingoid features and virilization. After a series of endocrine investigations, including urinary steroid profiling, a diagnosis of adrenocortical carcinoma was made. The treatment and prognosis of the disease are discussed.

A 7-year-old boy dying of acute encephalopathy.

A 7 year old Chinese boy died of a rapidly progressive encephalopathy after influenza infection. MRI showed bilateral and symmetrical lesions including the thalamus and brainstem tegmentum. The pathology of necrosis and vasculopathy were in keeping with acute necrotizing encephalopathy (ANE). ANE was first described in Japan and carries a high mortality and morbidity. A vasculopathy with breakdown of the blood-brain-barrier was incriminated but the pathogenesis remained obscure and autopsy studies have been limited. A review of the literature showed only nine postmortem reports in the acute stage. Symmetrical brain necrosis always involved the thalamus followed by the tegmentum of the pons and other regions. Exudative vasculopathy was commonly observed and often accompanied by endothelial cell necrosis. In the present case there was inflammatory fibrinoid vasculitis which has not been previously described.

Influenza-related hospitalisations in children.

AIM: To describe the disease burden, clinical pattern and outcome of influenza-related hospitalisations in children. METHODS: This is a retrospective study carried out in a regional hospital in Hong Kong. Children hospitalised with established diagnosis of influenza infection from January to June of 2005 were studied. Length of hospitalisation, demographic characteristics, symptoms, clinical diagnosis and complications of influenza infection were analysed. RESULTS: Influenza A infection accounted for 93.5% of these hospitalisations. Children less than 5 years of age comprised 70% of admission. Highest rate of admission occurred in May and April. One fourth of emergency admission during the study period and over 70% in the peak season was a result of influenza-related illness. Underlying medical disease was observed in 14.6% of children. Mean duration of hospitalisation was 3.0 days. Fever was the commonest presenting symptoms. Fever lasting for 7 days or more was observed in one-fifth of patients. Respiratory tract diseases (upper and lower) were the most frequent non-neurological diagnosis. Febrile convulsion was the complication observed in 27.6% of admission. One patient died as a result of acute necrotising encephalopathy. CONCLUSION: Influenza contributed to heavy health-care burden. Mortality was rare but did occur. Hospitalisations occurred in both healthy children and those with underlying chronic illness. Young children played an important role in such hospitalisations. Means to prevent influenza-associated morbidity and mortality especially among young children are needed.

The use of polymerase chain reaction assay versus conventional methods in detecting neonatal chlamydial conjunctivitis.

PURPOSE: To compare the performance of polymerase chain reaction versus conventional methods (cell culture and direct immunofluorescent assay) in diagnosing neonatal chlamydial conjunctivitis and their correlations to the severity of conjunctivitis. METHODS: Consecutive cases of neonatal conjunctivitis were recruited over a year. Both eyes were clinically graded according to the severity of conjunctivitis and investigated using the three aforementioned chlamydial tests. Neonatal chlamydial conjunctivitis was assumed if one of these three tests was positive and there was clinical improvement after treatment. Sensitivity and specificity of each of the tests were analyzed. RESULTS: Three hundred sixty-eight sets of chlamydial tests were done for 184 neonates. The percentage of positive results was 93.8% and 71.9% for polymerase chain reaction and conventional methods, respectively. Using positive results in either cell culture or direct immunofluorescent assay as a standard to diagnose neonatal chlamydial conjunctivitis, the sensitivity and specificity of polymerase chain reaction were 92.0% and 97.7%, respectively. If we used polymerase chain reaction as a standard, the sensitivity and specificity of cell culture were 73.3% and 99.7%, respectively. A discrepancy was noted in the number of positive results between polymerase chain reaction and conventional methods in milder disease. CONCLUSIONS: Polymerase chain reaction might have a higher sensitivity and similar specificity in diagnosing neonatal chlamydial conjunctivitis compared to conventional methods, and it has an additional advantage as a diagnostic tool in mild disease.

Diffusion-weighted imaging and proton magnetic resonance spectroscopy in perinatal hypoxic-ischemic encephalopathy: association with neuromotor outcome at 18 months of age.

We evaluated early diffusion-weighted imaging findings, the quantitative apparent diffusion coefficient, and magnetic resonance spectroscopy (the presence of lactate and ratios of N-acetylaspartate to total creatine and choline to total creatine) in the prediction of the 18-month neuromotor outcome of term newborns with hypoxic-ischemic encephalopathy. Conventional T1- and T2-weighted and diffusion-weighted imaging was performed in 20 asphyxiated term newborns, with additional basal ganglia magnetic resonance spectroscopy in 15 newborns between 2 and 18 days of life (mean 7.3 days). Neuromotor outcome was dichotomized into normal and abnormal for statistical analysis. Statistically significant differences in the ratios of N-acetylaspartate to total creatine, but not apparent diffusion coefficient values and ratios of choline to total creatine, were found between infants with a normal and an abnormal outcome (Mann-Whitney U-test, P = .010). There was a significant association between the presence of a lactate peak and an abnormal outcome (chi-square test, P = .017). The presence of a lactate peak for predicting an abnormal outcome had a sensitivity of 100% and a specificity of 80%, and the odds ratio was 37.4. Ischemic lesions were more conspicuous and/or extensive on diffusion-weighted imaging in all except one neonate. The presence of normal findings on both diffusion-weighted imaging and conventional magnetic resonance imaging is predictive of a normal neuromotor outcome, whereas lactate and a reduced ratio of N-acetylaspartate to total creatine in the basal ganglia, but not an apparent diffusion coefficient, are associated with an abnormal outcome at 18 months of age.