Publications by authors named "Chor-Kwan Ching"

20 Publications

  • Page 1 of 1

X-chromosome inactivation and PCDH19-associated epileptic encephalopathy: A novel PCDH19 variant in a Chinese family.

Clin Chim Acta 2021 Oct 28;521:285-288. Epub 2021 Jul 28.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region, China. Electronic address:

Background: Developmental and epileptic encephalopathy 9 (DEE9, MIM #300088) is an early onset seizure disorder associated with cognitive impairment and behavioral disturbances. It is caused by mutation in protocadherin 19 with an unusual X-linked inheritance selectively involving heterozygous females or mosaic hemizygous males, while hemizygous males are unaffected. Cellular interference was the postulated mechanism underlying the unusual inheritance pattern.

Case Report: We report a Chinese girl who presented with severe treatment refractory seizures at 26 months of age and was found heterozygous for a novel likely pathogenic missense variant NM_001184880.2:c.488T>A p.(Val163Glu) in PCDH19. Her younger sister, who was also heterozygous for the variant, was asymptomatic with normal development at the time of reporting at 37 months of age. X-chromosome inactivation study by androgen receptor gene methylation assay in DNA from peripheral leukocytes was performed which demonstrated somewhat skewed X-chromosome inactivation in the proband and extremely skewed X-chromosome inactivation in the asymptomatic younger sibling.

Conclusion: PCDH19-related seizure disorder has incomplete penetrance and variable expressivity. Further studies are required to determine the potential role of X-chromosome inactivation on the phenotypic variability and patient outcomes. Liberal referral for PCDH19 testing among female patients with early-onset seizures should be considered to enhance case detection.
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http://dx.doi.org/10.1016/j.cca.2021.07.023DOI Listing
October 2021

In-house multiplex ligation-dependent probe amplification assay for citrin deficiency: analytical validation and novel exonic deletions in SLC25A13.

Pathology 2021 May 24. Epub 2021 May 24.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong, China. Electronic address:

Citrin deficiency is one of the most common inborn errors of metabolism in East Asians, which may manifest as neonatal cholestasis, failure to thrive and dyslipidaemia, or recurrent hyperammonaemic encephalopathy. Its molecular diagnosis requires confirmation of the presence of biallelic pathogenic variants in SLC25A13 gene by sequencing, and analysis for a common insertion IVS16ins3kb. However, patients with compatible biochemical features but only one monoallelic pathogenic variant have remained a diagnostic challenge. Here we report the development, validation and application of a multiplex ligation-dependent probe amplification (MLPA) assay using an in-house oligonucleotide probemix and a customised Coffalyer.NET worksheet for detection of exonic copy number variations in SLC25A13. With this MLPA assay, we successfully identified the presence of a heterozygous exonic deletion in SLC25A13 in three of 15 (20%) unrelated individuals with only one monoallelic pathogenic variant detected using conventional methods. Three exonic deletions, two novel involving exon 14 and one reported involving exon 5, were subsequently confirmed with Sanger sequencing. In summary, we developed, evaluated, and demonstrated the clinical utility of an in-house MLPA assay to look for exonic deletions in SLC25A13 in patients with citrin deficiency. With the discovery of novel deletions, MLPA should be considered a test of choice for molecular diagnosis of citrin deficiency when the sequencing result is inconclusive.
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http://dx.doi.org/10.1016/j.pathol.2021.02.010DOI Listing
May 2021

Detection of 28 Corticosteroids in Pharmaceutical and Proprietary Chinese Medicinal Products Using Liquid Chromatography-Tandem Mass Spectrometry.

J Chromatogr Sci 2021 May;59(6):548-554

Hospital Authority Toxicology Reference Laboratory, Room 1414, Block G, 2-10 Princess Margaret Hospital Road, Lai Chi Kok, Kowloon, Hong Kong.

With their potent anti-inflammatory effects, corticosteroids are popular adulterants in illicit health products for allergies, dermatitis and pain control. Their illegal supply over the counter is also a common practice for similar conditions. Prolonged, unsupervised usage of corticosteroids often leads to severe adverse effects including Cushing syndrome, adrenal insufficiency and immunosuppression. Confirming clinical suspicion of unsupervised corticosteroid usage is challenging. Apart from evaluating the adrenal function, identifying the concerned drug is the most direct proof of its consumption. While detecting corticosteroids or their metabolites in biological specimens is convincing evidence of their usage, such approach is analytically difficult. More importantly, this approach would not be useful if the patient has stopped taking the drug for some time-a situation that is often encountered clinically. We advocate a more direct approach by measuring corticosteroids in suspicious medicinal products. In the current study, a liquid chromatography-tandem mass spectrometry method for simultaneous detection of 28 corticosteroids in pharmaceutical and proprietary Chinese medicine products was developed and validated for the purpose. The method was applied to 388 cases of suspected unsupervised corticosteroids usage. Among 1,000 products tested, corticosteroids were found in 276 of them and confirmed the clinical suspicion.
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http://dx.doi.org/10.1093/chromsci/bmaa140DOI Listing
May 2021

McArdle disease presenting as abnormal liver function: biochemical, anatomical and genetic characterisation in the first genetically confirmed Chinese family with a novel splicing variant.

Pathology 2021 08 10;53(5):670-673. Epub 2020 Dec 10.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/j.pathol.2020.09.019DOI Listing
August 2021

Toxicity from illegitimate slimming agents - a 10-year case series at a tertiary toxicology laboratory in Hong Kong.

Clin Toxicol (Phila) 2021 May 22;59(5):426-432. Epub 2020 Sep 22.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Kowloon, Hong Kong.

Context: This retrospective case-series study aims to provide an overview of the clinical, biochemical and analytical findings in patients who presented with toxicity related to the use of illegitimate slimming agents in Hong Kong from the perspective of a tertiary referral toxicology laboratory.

Methods: All clinical cases referred to the Hospital Authority Toxicology Reference Laboratory, Hong Kong with clinical suspicion of illegitimate slimming agent-related toxicity between January 2008 and December 2017 were reviewed retrospectively. The use of illegitimate slimming agents included the use of (1) deregistered slimming agents, (2) drug analogues that were not registered drugs, (3) registered drugs not approved for the indication of weight reduction (whether prescribed by a doctor or not), and (4) prescription-only slimming agents without a doctor's prescription. Patients taking registered weight-reducing drugs prescribed by a doctor were excluded. Patient demographics, clinical features, relevant laboratory investigations, and toxicological findings were analyzed.

Results: From 2008 to 2017, a total of 346 patients were analytically confirmed by our laboratory to have clinical toxicity related to the use of illegitimate slimming agents. The median age of the patients was 27 years and 92.5% of the patients were female. The most common clinical presentations included psychiatric features, sympathomimetic toxicity, hypokalemia, and abnormal thyroid function tests. Fatal or severe clinical toxicity was observed in 10% of the cases. The major classes of drugs detected on our analytical platforms were stimulants (e.g., sibutramine), laxatives (e.g., anthraquinones), diuretics (e.g., hydrochlorothiazide), and thyroid hormones (e.g., animal thyroid tissue). These illegitimate slimming agents were obtained from various sources including the Internet, over-the-counter in community pharmacy, or unspecified local sources.

Discussion And Conclusions: The use of slimming agents is common worldwide; apart from taking registered slimming agents prescribed by registered practitioners, many users obtain slimming agents from various illegitimate sources. The unregulated use of these drugs can be associated with significant clinical toxicity. This study provides a current landscape of illegitimate slimming agent toxicity in Hong Kong to frontline clinicians and other toxicology professionals. Collaboration between clinicians, laboratories, and government authorities would be imperative to prevent further health adversities related to the misuse of these agents.
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http://dx.doi.org/10.1080/15563650.2020.1822529DOI Listing
May 2021

Determination of cerebrospinal fluid adenosine deaminase activity cut-off for the diagnosis of tuberculous meningitis in Hong Kong.

J Clin Pathol 2020 Dec 18;73(12):800-802. Epub 2020 May 18.

Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Kowloon, Hong Kong.

Aims: Tuberculous meningitis (TBM) is a severe infection which may lead to serious complication and mortality. Prompt diagnosis and treatment are essential. There is a need for a simple and fast laboratory test to differentiate TBM from other causes.

Methods: Retrospective review was conducted for cerebrospinal fluid adenosine deaminase (CSF-ADA) activity which was measured at the Chemical Pathology Laboratory of Princess Margaret Hospital, the sole centre providing such service in Hong Kong, for 51 patients with suspected meningitis from nine local hospitals between June 2014 and July 2017. TBM diagnosis was defined by positive culture and/or nucleic acid amplification test result of complex in CSF.

Results: CSF-ADA activity was significantly higher in the TBM group (8.6±2.1 IU/L, n=8) than that of the non-TBM group (2.8±5.9 IU/L, n=43). The optimal clinical cut-off of 5.1 U/L for TBM diagnosis in our laboratory yielded 100% sensitivity, 91% specificity, positive likelihood ratio of 10.8 and negative likelihood ratio of 0. In rare circumstance, false elevation may be seen in non-tuberculous cause, such as central nervous system lymphoma and fungal infection.

Conclusions: We recommend the use of CSF-ADA activity, which is a simple, fast and robust test for early differentiation of TBM from other causes, to facilitate timely initiation of antituberculous treatment and potentially improve patients' outcome.
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http://dx.doi.org/10.1136/jclinpath-2019-206397DOI Listing
December 2020

Simultaneous detection of 24 oral antidiabetic drugs and their metabolites in urine by liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Mar 3;1141:122020. Epub 2020 Feb 3.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong. Electronic address:

Drugs are the most frequent cause of hypoglycemia. Though the drug history is usually obvious in diabetic patients, the diagnosis could be a challenge in patients without a history of such exposure. Screening for oral antidiabetic drugs has been recommended as part of the hypoglycemia workup in patients without diabetes. Many published analytical methods of oral antidiabetic agents were usually of limited coverage and restricted to parent drugs only. In the current study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical system for the simultaneous detection of 24 oral antidiabetic drugs and their metabolites in urine was established and validated. The method covered both conventional as well as the newer antidiabetic drugs such as dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors. Following sample preparation by solid phase extraction, analytes were detected by LC-MS/MS with multiple reaction monitoring triggered enhanced product ion scan. The method was successfully applied to 233 cases of unexplained hypoglycemia, with 83 oral antidiabetic drugs detected in 51 of the urine samples.
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http://dx.doi.org/10.1016/j.jchromb.2020.122020DOI Listing
March 2020

Practical Aspects in Genetic Testing for Cardiomyopathies and Channelopathies.

Clin Biochem Rev 2019 Nov;40(4):187-200

Department of Pathology, Princess Margaret Hospital, Hong Kong.

Genetic testing has an increasingly important role in the diagnosis and management of cardiac disorders, where it confirms the diagnosis, aids prognostication and risk stratification and guides treatment. A genetic diagnosis in the proband also enables clarification of the risk for family members by cascade testing. Genetics in cardiac disorders is complex where epigenetic and environmental factors might come into interplay. Incomplete penetrance and variable expressivity is also common. Genetic results in cardiac conditions are mostly probabilistic and should be interpreted with all available clinical information. With this complexity in cardiac genetics, testing is only indicated in patients with a strong suspicion of an inheritable cardiac disorder after a full clinical evaluation. In this review we discuss the genetics underlying the major cardiomyopathies and channelopathies, and the practical aspects of diagnosing these conditions in the laboratory.
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http://dx.doi.org/10.33176/AACB-19-00030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892704PMC
November 2019

Case Report: The first probable Hong Kong Chinese case of -related acute recurrent rhabdomyolysis in a boy with two novel variants.

F1000Res 2019 2;8:1566. Epub 2019 Sep 2.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong, Laichikok, Hong Kong.

Recurrent rhabdomyolysis is frequently ascribed to fatty acid ß-oxidation defects, mitochondrial respiratory chain disorders and glycogen storage-related diseases. In recent years, autosomal recessive mutations have been identified as a prevailing cause of severe rhabdomyolysis in children in Western countries. We report the first probable Hong Kong Chinese case of recurrent severe rhabdomyolysis in early childhood caused by variants. Compound heterozygous novel variants NM_145693.2(LPIN1):c.[1949_1967dupGTGTCACCACGCAGTACCA]; [2410G>C] (p.[Gly657Cysfs*12];[Asp804His]) were detected. The former variant was classified as likely pathogenic while the latter variant was classified as a variant of uncertain significance (VUS) based on the guideline published by the American College of Medical Genetics and Genomics (ACMG) in 2015. Although the genetic findings were inconclusive, the patient's presentation was compatible with LPIN1-related acute recurrent rhabdomyolysis, and the patient was treated as such. The early recognition, timely diagnosis and management of this condition are important to avoid fatal consequences. To our knowledge, there has been no previous report in the English-language literature of a child with Chinese ethnicity and -related acute recurrent rhabdomyolysis (MIM #268200).  Functional characterization of the novel variants detected in this study are warranted in future studies.
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http://dx.doi.org/10.12688/f1000research.20343.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823901PMC
June 2020

First case of genetically confirmed CLN3 disease in Chinese with cDNA sequencing revealing pathogenicity of a novel splice site variant.

Clin Chim Acta 2018 Nov 24;486:151-155. Epub 2018 Jul 24.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong. Electronic address:

Background: Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) is a hereditary progressive neurodegenerative disease well documented among Caucasians, but such clinical data and genetic characterization is lacking among Asian populations.

Patient And Methods: A 13-year-old Chinese girl presented for diagnostic evaluation with retinitis pigmentosa, generalised tonic-clonic seizure and cerebellar ataxia. Electron microscopy of whole blood and skin biopsy, and mutation analysis of CLN3 gene with genomic DNA and cDNA, were performed.

Results: Electron microscopy showed vacuolated lymphocytes, and characteristic patterns in eccrine glands suggestive of neuronal ceroid lipofuscinosis. Sequencing of genomic DNA showed homozygous splice site variant NM_000086.2(CLN3):c.906+6T>G, and the pathogenicity of which was confirmed by cDNA sequencing to demonstrate the deletion of a transmembrane domain of the CLN3 protein. The mutant protein was predicted to adversely affect ligand binding of CLN3 as a lysosomal membrane protein.

Conclusions: Here we report the first genetically confirmed CLN3 disease in Chinese, with a novel splice site variant with proposed pathogenetic mechanism relating gene and protein, and highlights the potential ethnic differences in the mutation spectrum. We wish to establish the importance of clinical awareness and laboratory diagnosis of CLN3 disease, especially in the promising age of gene therapy.
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http://dx.doi.org/10.1016/j.cca.2018.07.040DOI Listing
November 2018

Retrospective Study of the Characteristics of Anticoagulant-Type Rodenticide Poisoning in Hong Kong.

J Med Toxicol 2018 09 23;14(3):218-228. Epub 2018 Apr 23.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Kowloon, Hong Kong, People's Republic of China.

Introduction: Warfarin- and superwarfarin-type anticoagulants are commonly used as rodenticides. Exposure to these agents, especially superwarfarins with long-acting anticoagulant effect, can cause life-threatening coagulopathy in humans. Most superwarfarin poisoning cases had an obvious history of exposure, though occult cases without exposure history have also been reported. The current study aims to examine anticoagulant-type rodenticide poisoning in Hong Kong and to identify the similarities and differences between patients with known exposure history and those whose exposure is recognized only through laboratory testing.

Methods: The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. This was a retrospective cohort study of all patients with biochemically confirmed anticoagulant-type rodenticide exposure, from 2010 to 2014.

Results: Superwarfarin was the most common group of anticoagulant-type rodenticides identified (87.8%), in which bromadiolone and brodifacoum were the most frequently encountered. Among the 41 cases identified, 31 had an obvious exposure history, and 10 were occult poisoning in which the context of exposure remained unidentified. All occult poisoning patients without exposure history presented with bleeding events. These occult poisoning cases often went unrecognized by frontline clinicians, leading to delayed investigation and initiation of treatment. This group of patients was associated with a longer time to diagnose coagulopathy (p < 0.001) and confirm rodenticide poisoning (p < 0.05), a higher rate of international normalized ratio (INR) rebound after initiation of antidote (p < 0.001), and a longer time needed for normalizing INR (p < 0.05).

Conclusion: Occult superwarfarin poisoning is an important yet under-recognized differential cause of unexplained coagulopathy. A high index of clinical suspicion and availability of specialized toxicological test for superwarfarins play a vital role in diagnosis and early initiation of appropriate management. The underlying cause of such poisoning remains obscure and warrants further study.
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http://dx.doi.org/10.1007/s13181-018-0660-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097974PMC
September 2018

Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

Br J Clin Pharmacol 2018 Jan 4;84(1):172-178. Epub 2017 Oct 4.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong.

Aims: Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong.

Methods: The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively.

Results: A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects.

Conclusions: Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem.
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http://dx.doi.org/10.1111/bcp.13420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736835PMC
January 2018

Severe rhabdomyolysis and acute kidney injury associated with methoxphenidine.

Clin Toxicol (Phila) 2016 Jun 23;54(5):464-5. Epub 2016 Mar 23.

c Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital , Laichikok, Hong Kong Special Administrative Region , ROC.

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http://dx.doi.org/10.3109/15563650.2016.1157724DOI Listing
June 2016

NMR-based urinalysis for beta-ketothiolase deficiency.

Clin Chim Acta 2015 Jan 4;438:222-5. Epub 2014 Sep 4.

Department of Pathology, Princess Margaret Hospital, Hong Kong, China.

Background: Beta-ketothiolase deficiency is a rare inborn errors of metabolism (IEM) affecting the catabolism of isoleucine, characterized by severe ketoacidosis in children of 6 to 24months old. A prompt diagnosis is of paramount importance as the metabolic decompensation can be effectively reverted by glucose infusion and health outcomes are improved on a protein-restricted diet. Currently, majority of the laboratory diagnosis were made based on mass-spectrometry and molecular genetics while little is mentioned on the advancement of nuclear magnetic resonance (NMR) spectroscopy for the diagnosis of this condition.

Case: We report a case of beta-ketothiolase deficiency in a 1-y-old Chinese boy who presented with repeated vomiting, impaired consciousness and severe ketoacidosis. NMR urinalysis detected excessive amount of butanone (a disease specific marker of beta-ketothiolase deficiency), tiglylglycine, (intermediate of isoleucine catabolism) and ketones. Diagnosis of beta-ketothiolase deficiency was further established by molecular genetic studies of ACAT1 gene of the proband.

Conclusions: This case illustrated that NMR-based urinalysis is complementary to organic acid analysis for diagnosis of beta-ketothiolase deficiency. The operation of NMR is simple and fast; sample preparation is a two-step procedure while the NMR acquisition is automatic and usually takes <15min. We envisage that NMR analysis will become more available in clinical laboratories and will play an important role in acute pediatric care.
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http://dx.doi.org/10.1016/j.cca.2014.08.041DOI Listing
January 2015

Simultaneous detection of 22 toxic plant alkaloids (aconitum alkaloids, solanaceous tropane alkaloids, sophora alkaloids, strychnos alkaloids and colchicine) in human urine and herbal samples using liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2013 Dec 22;942-943:63-9. Epub 2013 Oct 22.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong.

A liquid chromatography-tandem mass spectrometry method for simultaneous detection of 22 toxic plant alkaloids, including aconitum alkaloids and their hydrolyzed products (aconitine, hypaconitine, mesaconitine, yunaconitine, crassicauline A, benzoylaconine, benzoylmesaconine, benzoylhypaconine, deacetylyunaconitine, deacetylcrassicauline A), solanaceous tropane alkaloids (atropine, anisodamine, scopolamine, anisodine), sophora alkaloids (matrine, sophoridine, oxymatrine, cytisine, N-methylcytisine), strychnos alkaloids (brucine, strychnine) and colchicine, in herbal and urine samples was developed and validated. Following sample preparation by liquid-liquid extraction, chromatographic separation was achieved on Eclipse XDB C8 column. Identification was based on two multiple reaction monitoring transitions and the relative ion intensity. Method selectivity was demonstrated. The limits of detection were 5ng/mL for all analytes, except 50ng/mL for cytisine. The herbal matrix effects ranged from 89% to 118%, whereas the urine matrix effects were between 91% and 109% for all analytes except cytisine (57%) and N-methylcytisine (67%). The urine extraction recovery ranged from 74% to 110% for all analytes, except cytisine (15%) and oxymatrine (30%). With the good extraction efficiency of the other major sophora alkaloids, the relatively low extraction recovery of the minor sophora alkaloids cytisine and oxymatrine did not affect identification of sophora alkaloids as a group. Carry-over was minimal at less than 0.1%. The method was successfully applied in analysis of 170 cases of suspected herbal poisoning, with aconitum alkaloids, sophora alkaloids, solanaceous tropane alkaloids, and strychnos alkaloids being detected in 53, 42, 18, and 6 cases, respectively.
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http://dx.doi.org/10.1016/j.jchromb.2013.10.020DOI Listing
December 2013

Arginase deficiency with new phenotype and a novel mutation: contemporary summary.

Pediatr Neurol 2012 Oct;47(4):263-9

Department of Radiology, Tuen Mun Hospital, Hong Kong Special Administrative Region, China.

In areas without expanded newborn screening, instead of presenting neonatally, patients with arginase deficiency typically present with spastic paraplegia in early childhood. Diagnosis of this rare neurometabolic disease poses the first challenge because it is often misdiagnosed as cerebral palsy during initial stages. We describe arginase deficiency in a 20-year-old woman with spastic paraplegia, progressive dystonia, dementia, peripheral neuropathy, epilepsy, liver cirrhosis, and non-B/non-C hepatocellular carcinoma. A novel homozygous mutation NM_000045.2 (ARG1):c.673del (p.Arg225GlyfsX5) was detected. We suggest that all children presenting with progressive neurodegeneration or spastic paraplegia in the absence of risk factors for cerebral palsy should be screened for inborn errors of metabolism, including arginase deficiency. For monitoring urea cycle defects, noninvasive imaging screening for liver fibrosis and hepatocellular carcinoma can help ensure early detection, with potential treatment implications.
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http://dx.doi.org/10.1016/j.pediatrneurol.2012.06.012DOI Listing
October 2012

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

J Clin Pathol 2012 Dec 10;65(12):1141-5. Epub 2012 Aug 10.

Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong SAR, China.

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.
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http://dx.doi.org/10.1136/jclinpath-2012-200837DOI Listing
December 2012

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong.

Br J Clin Pharmacol 2012 May;73(5):795-800

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Lai Chi Kok, Hong Kong, China.

Aims: The current study aims to examine the problem of adulteration of herbal antidiabetic products with undeclared pharmaceuticals, including both registered and banned drugs.

Methods: All cases involving use of adulterated herbal antidiabetic products referred to a tertiary centre for clinical toxicology analysis from 2005 to 2010 inclusive were retrospectively reviewed. The patients' demographic characteristics, clinical presentations, medical history, drug history and the analytical findings of the herbal antidiabetic products were studied.

Results: A total of 27 cases involving use of 29 adulterated herbal antidiabetic products were identified. Seventeen of the patients (63%) had clinical toxicities associated with the illicit products. Hypoglycaemia was the most common adverse effect, followed by lactic acidosis. Analysis of the 29 illicit herbal antidiabetic products revealed eight undeclared registered or banned oral antidiabetic agents, namely glibenclamide (n= 22), phenformin (n= 18), metformin (n= 6), rosiglitazone (n= 6), gliclazide (n= 2), glimepiride (n= 2), nateglinide (n= 1) and repaglinide (n= 1). Non-antidiabetic drugs were also detected in some products. Up to four adulterants were detected within the same product.

Conclusions: Adulteration of herbal antidiabetic products with undeclared pharmaceuticals is a significant yet under-recognized problem. Patients taking these illicit products could be at risk of potentially fatal adverse effects. It is important to educate the public to avoid taking pCMs of dubious source. Effective regulatory measures should be put in place to address the problem.
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http://dx.doi.org/10.1111/j.1365-2125.2011.04135.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403207PMC
May 2012

Analysis of inborn errors of metabolism: disease spectrum for expanded newborn screening in Hong Kong.

Chin Med J (Engl) 2011 Apr;124(7):983-9

Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong SAR, China.

Background: Data of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.

Methods: The laboratory records of plasma amino acids, plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed.

Results: Among the cohort, 43 patients were diagnosed of IEM, including 30 cases (69%) of amino acidemias (predominantly citrin deficiency, hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency and tyrosinemia type I), 5 cases (12%) of organic acidemias (predominantly holocarboxylase synthetase deficiency) and 8 cases (19%) of fatty acid oxidation defects (predominantly carnitine-acylcarnitine translocase deficiency). The incidence of classical IEM in Hong Kong was roughly estimated to be at least 1 case per 4122 lives births, or 0.243 cases per 1000 live births. This incidence is similar to those reported worldwide, including the mainland of China. The estimated incidence of hyperphenylalaninemia was 1 in 29 542 live births.

Conclusions: Our data indicate that it is indisputable for the introduction of expanded newborn screening program in Hong Kong. Since Hong Kong is a metropolitan city, a comprehensive expanded newborn screening program and referral system should be available to serve the neonates born in the area.
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April 2011

A novel mitofusin 2 gene mutation causing Charcot-Marie-Tooth type 2A disease in a Chinese family.

Chin Med J (Engl) 2010 Jun;123(11):1466-9

Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong, China.

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June 2010
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