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ABSTRACT: Hyperekplexia is a rare neurologic disorder, characterized by excessive startle response to unexpected stimuli. There are 3 cardinal features: generalized stiffness immediately after birth that normalizes during the first year of life; excessive startle reflex to unexpected (particularly auditory) stimuli; and a short period of generalized stiffness following the startle response while patient cannot elicit voluntary movements. Awareness of this condition will avoid misdiagnosis of disorders like epilepsy. Clonazepam is an effective medical treatment. We report a patient whose frequent falls triggered by sudden noise or tactile stimuli was initially misdiagnosed as epilepsy. The clinical diagnosis was subsequently revised to hyperekplexia and confirmed by mutation analysis of the GLRA1 gene, which showed c.497G>C (p.Cys166Ser) and c.526delG (p.Asp176Metfs*16). Both of them are novel mutations. His response to clonazepam is dramatic and has been able to engage in sports and social activities.
Journal of child neurology 11/2012; · 1.59 Impact Factor
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Chloe Miu Mak,
Wai-Kwan Siu,
Chun-Yiu Law,
Chi-Keung Wong,
Hon-Kit Lee,
Sam Yeung,
Chak-On Sham,
Kong Tse,
Hencher Han-Chih Lee,
Sammy Pak-Lam Chen,
Chor-Kwan Ching,
Chui-Kwan Au, Wing-Tat Poon,
Ching-Wan Lam,
Ngai-Shan Kwong,
Albert Yan-Wo Chan
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ABSTRACT: 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.
Journal of clinical pathology 08/2012; · 2.43 Impact Factor
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ABSTRACT: Aconite poisoning is a severe, life-threatening poisoning related to the use of traditional Chinese medicine (TCM). Despite current legislation, repeated poisoning cases are steadily encountered.
The aim of the study was to summarize the clinical features and to elucidate the causative and contributory factors leading to aconite poisoning.
This study was conducted within the Hospital Authority Toxicology Reference Laboratory, which is the sole tertiary referral clinical toxicology laboratory in Hong Kong. This retrospective study reviewed all confirmed aconite poisoning cases handled by a clinical toxicology laboratory between April 2004 and July 2009. The diagnosis in all cases was confirmed biochemically by detecting aconitum alkaloids in urine specimens. Additionally, herbal specimens were morphologically identified and herbal formulae were studied and transcribed. The cause of poisoning for each case was determined whenever possible.
Fifty-two cases were examined in this aconite poisoning case series. Neurological, cardiovascular and gastrointestinal toxicities were encountered in 49 (94.2%), 46 (88.5%) and 31 (59.6%) patients, respectively. The poisoning was severe in 6 (11.5%) patients, moderate in 17 (32.7%) patients and mild in 29 (55.8%) patients. Amongst 44 patients (84.6%) in whom the underlying reasons of poisoning could be determined, four major causes were found. These included overdose - prescription of a higher than recommended dosage of aconite herbs in 17 (32.7%) cases; 'hidden' poisoning (the aconite herb was not prescribed but dispensed inadvertently) in 17 (32.7%) cases; usage of inadequately processed herbs in 7 (13.5%) cases; and dispensary error in 2 (3.9%) cases. No case fatality was recorded.
In the majority of cases in this series, the causes of poisoning can be traced to poor-quality herbs, poor quality of prescription practice, or dispensary errors. The quality issues of TCM practice should be critically addressed to minimize this poisoning threat.
Drug Safety 05/2012; 35(7):575-87. · 3.63 Impact Factor
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ABSTRACT: Proopiomelanocortin (POMC) is the polypeptide precursor of several biologically active melanocortin peptides that have important roles in the regulation of food intake and energy homeostasis, adrenal steroidogenesis, melanocyte stimulation, and immune modulation. Mutation of the POMC gene has been associated with adrenal insufficiency, early-onset obesity, and red hair pigmentation. We describe an Indian boy with secondary hypocortisolism, hyperphagia, early-onset obesity, and skin pigmentation problem. Genetics analysis revealed a novel homozygous mutation in the POMC gene (p.Arg86Term). The boy also had central hypothyroidism in addition to the secondary hypocortisolism. Genetics analysis for the POMC gene should be considered in patients with secondary hypocortisolism, early-onset obesity, and pigmentary problems.
Journal of pediatric endocrinology & metabolism: JPEM 01/2012; 25(1-2):175-9. · 0.88 Impact Factor
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Chloe Miu Mak,
Ching-wan Lam,
Nai-chung Fong,
Wai-kwan Siu,
Han-chih Hencher Lee,
Tak-shing Siu,
Chi-kong Lai,
Chun-yiu Law,
Sui-fun Tong, Wing-tat Poon,
David Shu-yan Lam,
Ho-leung Ng,
Yuet-ping Yuen,
Sidney Tam,
Tak-lun Que,
Ngai-shan Kwong,
Albert Yan-wo Chan
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ABSTRACT: 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.
Journal of Human Genetics 06/2011; 56(8):617-21. · 2.57 Impact Factor
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Pathology 04/2011; 43(3):273-4. · 2.38 Impact Factor
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ABSTRACT: To evaluate an algorithmic approach involving a multidisciplinary team for causality assessment of suspected herb-induced liver injury (HILI) cases and to compare the causality score using this multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM).
A team consisting of hepatologist, clinical toxicologist, analytical toxicologist, and Chinese medicine (CM) pharmacist was formed to do causality assessment based on a protocol for suspected HILI cases. The likelihood of the diagnosis of individual case was first assessed systematically by a hepatologist and clinical toxicologist independently after collecting information about four aspects: (1) clinical course, (2) exclusion of alternative causes, (3) quality of the prescription and herbal product by examining the CM prescriptions and analysis of biological and herb samples, (4) scientific support on comprehensive literature review on English and Chinese medical database, and subsequently concluded in a consensus meeting held by the multidisciplinary team. The final causality score of each patient was compared with the likelihood of causality as assessed by RUCAM.
Between 2005 and 2007, 48 consecutive patients with suspected HILI were enrolled and 21 patients were excluded due to the establishment of an alternative cause of liver impairment or the lack of any information on the herbs taken. Twenty-seven patients were recruited, among them 15 consumed Chinese herbal medicines, 10 used proprietary Chinese medicinal products, and 2 used both. The concordance between the causality assessment of the hepatologist and clinical toxicologist was moderate (weighted κ = 0.48, 95%CI 0.30-0.66). The causality assessment process concluded that the likelihood of HILI was "highly probable" in 5 cases and "probable" in 12, whereas there were 5 "highly probable" and 16 "probable" cases as assessed by RUCAM. The causality assessment by the multidisciplinary approach and RUCAM also showed moderate agreement (weighted κ= 0.51, 95%CI 0.22-0.81).
A multidisciplinary approach using defined algorithms is a scientific approach in causality assessment for HILI. Further study is needed to assess its accuracy and applicability.
Clinical Toxicology 01/2011; 49(1):34-9. · 2.22 Impact Factor
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ABSTRACT: Prolonged intake of aristolochic acid (AA) has been shown to be associated with the development of certain renal disorders. Renal tubular atrophy and interstitial fibrosis are the early symptoms of AA nephropathy. The symptoms were observed in rats that were dosed with AA at a dosage of 10 mg/kg/day for 1 month. Apart from the renal tubular atrophy and interstitial fibrosis, AA-DNA adducts were detected in the rat kidney tissue. Differentiated proteins were identified in the kidney tissues from proteomics investigations. The upregulated proteins identified included ornithine aminotransferase, sorbitol dehydrogenase, actin, aspartoacylase, 3-hydroxyisobutyrate dehydrogenase, and peroxiredoxin-1. Downregulated proteins such as ATP synthase subunit β, glutamate dehydrogenase 1, regucalcin, glutamate-cysteine ligase regulatory subunit, dihydropteridine reductase, hydroxyacyl-coenzyme A dehydrogenase, voltage-dependent anion-selective channel protein 1, prohibitin, and adenylate kinase isoenzyme 4 were also identified. Several identified protein markers were found to have biological and medical significance.
Analytical and Bioanalytical Chemistry 12/2010; 399(10):3431-9. · 3.78 Impact Factor
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ABSTRACT: Sibutramine, or its structurally related analogs, is often found as an adulterant in proprietary herbal slimming products in Hong Kong. A few solitary case reports of sibutramine-associated psychosis have been published since 2000. As the only tertiary referral center for clinical toxicology analysis in Hong Kong, we noticed that psychosis was an unusually common feature in patients taking "herbal slimming products" adulterated with sibutramine or its structurally related analogs over the past 5 years.
To examine the association between psychosis and the use of sibutramine-adulterated herbal products, in an attempt to elucidate this possible adverse drug reaction.
This retrospective study reviewed all cases hospitalized with psychotic symptoms confirmed to have used herbal slimming products adulterated with sibutramine, or its analogs, between January 2004 and October 2009. The cases' clinical features, outcome, drug history, and analytical findings of the offending slimming products were studied. Results. Among the 16 confirmed cases, 15 (94%) were female; the median age was 19 years (range: 15-47). Auditory hallucination was documented in 10 (63%), visual hallucination in 6 (38%), persecutory ideas in 6 (38%), delusions in 4 (25%), and suicidal ideation in 2 (13%). For 20 "herbal" slimming products analyzed, 16 were found to have been adulterated with sibutramine, 2 with N-desmethyl-sibutramine, and 1 with N-bisdesmethyl-sibutramine. Other concomitant adulterants were also found and included phenolphthalein in 9, fenfluramine, mazindol, animal thyroid tissue in 2, hydrochlorothiazide and spironolactone in 1. Eight patients disclosed the source of the products: four through the Internet, one obtained over-the-counter locally, with three acquired outside Hong Kong.
Slimming products claimed "herbal" in origin could often be adulterated with sibutramine and other Western medications. We observed an association between the use of these products and psychotic features. Further studies are warranted to study whether these adverse events are an uncommon adverse drug reaction of sibutramine.
Clinical Toxicology 10/2010; 48(8):832-8. · 2.22 Impact Factor
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ABSTRACT: Fructus Psoraleae (FP) is used by herbalists for the treatment of postmenopausal osteoporosis, vitiligo, and psoriasis. It is used alone, or in combination with other herbs, in some countries in the form of proprietary medicine. It is recognized as one of the emerging hepatotoxins and here we report three cases of acute hepatitis after exposed to FP and its related proprietary medicine. It seems possible that psoralen and its related chemicals may be responsible for the hepatotoxicity. Decoction with other herbs may result in higher concentration of toxic constituents and in more severe liver injury. In summary, FP is associated with hepatotoxicity in some individuals. Pharmacovigilance for the potential side effects of herbal products is necessary.
Clinical Toxicology 08/2009; 47(7):683-5. · 2.22 Impact Factor
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ABSTRACT: A sensitive high-performance liquid chromatography method with fluorescence detection (HPLC-FLD) for the determination of DNA adducts induced by nephrotoxic and carcinogenic aristolochic acid (AA) is presented. The DNA adduct of AAII (dA-AAII) was synthesized by in vitro incubation, purified by preparative HPLC, characterized using fluorescence spectroscopy and high-resolution mass spectrometry, and was used as the biomarker for AA exposure in rats. The developed HPLC-FLD method was validated and applied for the determination of dA-AAII in rat kidney tissues. The method provided a detection limit of 18.3fmol, which allowed the detection of dA-AAII in the rat kidney tissue samples collected after a single oral dose of AA. dA-AAII was detected in the kidney DNA digestion extracts of the rats that were dosed with AA at 5mg/kg and 30mg/kg at concentrations of 6.2+/-1.1 and 41.3+/-8.0 dA-AAII per 10(9) normal dA, respectively.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 03/2009; 877(10):848-52. · 2.78 Impact Factor
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ABSTRACT: Aristolochic acid (AA), derived from the herbal genus Aristolochia and Asarum, has recently been shown to be associated with the development of nephropathy. Upon enzyme activation, AA is metabolized to the aristolactam-nitrenium ion intermediate, which reacts with the exocyclic amino group of the DNA bases via an electrophilic attack at its C7 position, leading to the formation of the corresponding DNA adducts. The AA-DNA adducts are believed to be associated with the nephrotoxic and carcinogenic effects of AA. In this study, liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS) was used to identify and quantify the AA-DNA adducts isolated from the kidney and liver tissues of the AA-dosed rats. The deoxycytidine adduct of AA (dC-AA) and the deoxyadenosine-AA adduct (dA-AA) were detected and quantified in the tissues of rats with one single oral dose (5mg or 30mg AA/kg body weight). The deoxyguanosine adduct (dG-AA), however, was detected only in the kidney of rats that were dosed at 30mg AA/kg body weight for three consecutive days. The amount of AA-DNA adducts found in the rats correlated well with the dosage.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 10/2008; 646(1-2):17-24. · 2.85 Impact Factor
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ABSTRACT: In Hong Kong, Chinese medicine is popular and coexists with orthodox Western medicine. Despite a long history of use, many herbs have not been submitted to rigorous scientific testing and there are reports of hepatotoxicity. We describe a woman who developed acute hepatitis after drinking an herbal remedy containing Teucrium viscidum.
A previously healthy 51-year-old woman was admitted to a regional hospital because of jaundice, with complaints of nausea, vomiting, and tea-colored urine for three days prior to admission. She denied any recent ingestion of known hepatotoxins, but she had consumed an herbal remedy for low back pain for three days before the onset of symptoms. She was icteric and had a serum total bilirubin level of 11.4 mg/dL, alanine aminotransferase of 2620 U/L, aspartate aminotransferase of 1876 U/L, and alkaline phosphatase level of 186 U/L. Discontinuation of the herbal remedy resulted in normalization of the liver enzymes two months later.
This is the first report of hepatitis probably related to use of Teucrium viscidum. The herb is infrequently used in Chinese medicine for treatment of rheumatic and bleeding disorders. T. viscidum contains teucvin, similar to other Teucrium species and is related to T. chamaedrys, commonly known as germander, which is a well documented cause of hepatotoxicity.
Our findings suggest that Teucrium viscidum can cause hepatotoxicity similar to that of germander.
Clinical Toxicology 05/2008; 46(9):819-22. · 2.22 Impact Factor
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ABSTRACT: A new herbal health product marketed for enhancing erectile function, namely Power58 Platinum, was purchased over-the-counter in Hong Kong. The product was tested for adulteration with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. A new analogue of vardenafil, in which the N-ethylpiperazine ring and the sulphonyl group were removed from the vardenafil structure, was identified in the product.
Journal of Pharmaceutical and Biomedical Analysis 04/2008; 46(4):804-7. · 2.97 Impact Factor
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ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal disease in childhood. The association of microangiopathic hemolytic anemia, schistocytes, and thrombocytopenia without fever, neurologic, and renal involvement is sufficient to suspect TTP at an early stage for prompt plasma infusion or exchange therapy. TTP has been increasingly described especially in association with systemic lupus erythematosus (SLE). We report the youngest Chinese boy who presented his SLE with TTP and subsequently experienced 9 relapses of TTP in a 2-year period. SLE disease activity index was low during his TTP relapses and therefore alertness of TTP relapse is required even in a relatively inactive period of SLE. TTP should be recognized even without renal or neurologic features and can respond to plasma therapy.
JCR Journal of Clinical Rheumatology 09/2007; 13(4):224-8. · 1.36 Impact Factor
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Clinica Chimica Acta 01/2007; 374(1-2):151-2. · 2.54 Impact Factor
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ABSTRACT: Poisoning from aconite occurs worldwide as a result of misuse of the potent plant. Laboratory investigation into suspected intoxication cases is challenging because the content of toxic aconitum alkaloids varies depending on the plant source, market processing, dosing protocol, hydrolytic degradation, and metabolic transformation. Using a triple-quadrupole tandem mass spectrometer, a group screening method was developed based on the mass-fragmentographic scheme of common aconitum alkaloids. The precursor-ion scans of m/z 105 and 135 permitted selective profiling of 14-O-benzoyl-norditerpenoids and the 14-O-anisoyl-norditerpenoids, respectively. Gradient reversed-phase liquid chromatography minimized coelution of isobaric compounds. The screening protocol was applied to a clinical investigation of suspected herbal poisoning. In total, 15 urine samples were thus screened positive for aconitum alkaloid over 5 years. The diagnoses of aconite poisoning in 11 patients were firmly established based on the known prescription history and the positive urine finding. In four patients, without aconitum herbs being listed in the herbal prescriptions, contamination of the herbal remedies by aconite was suspected to be the hidden cause of their acute poisoning. Yunaconitne, a highly toxic aconitum alkaloid, was thus identified in human urine for the first time. The group screening method of aconitum alkaloids in urine is an important diagnostic aid for acute poisoning by aconites of an unclear origin.
Journal of analytical toxicology 10/2006; 30(7):426-33. · 2.02 Impact Factor
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ABSTRACT: A HPLC method was developed and applied to analyze aristolochic acids (AA-I and AA-II) in Chinese medicinal herbs. The herb samples were extracted by using ultrasonication with the extraction efficiency of better than 82%. Extracts were then filtered and injected onto a C18 column eluting under a gradient program using methanol and water-containing 0.5% acetic acid. The method with the detection limits of 1.33 ng for AA-I and 7.29 ng for AA-II per injection was successfully applied for the analysis of traditional Chinese medicine (TCM) and related products and differentiation of Chinese medicinal herbs that have previously been misused and caused toxicological effects. The developed protocol provided an example that analysis of selected component markers could serve for health security and quality control of TCM consumption.
Analytica chimica acta 09/2006; 576(1):112-6. · 4.31 Impact Factor
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ABSTRACT: Numerous vitamin supplements are available over-the-counter to the general public. Some such supplements are available as candy-like chewable preparations to encourage consumption by children. We report 3 cases of overdose of such preparations. Each patient had taken an estimated 200,000 to 300,000 IU of vitamin A. Their circulating vitamin A (retinol and retinyl palmitate) concentrations were monitored over a 6-month period. There were no clinical or biochemical complications noted. However, there were marked increases in both retinol and retinyl palmitate concentrations above age-related reference ranges. In particular, it took 1 to 3 weeks for the serum retinol concentrations to peak and many months for them to normalize. Parents should be warned about the dangers of excessive vitamin consumption. Clinicians should be aware of the late peak in serum retinol concentrations, which may lead to late complications of vitamin A overdose.
PEDIATRICS 09/2006; 118(2):820-4. · 4.47 Impact Factor
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Clinica Chimica Acta 03/2006; 364(1-2):361-2. · 2.54 Impact Factor
