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Background Aromatic L-amino acid decarboxylase deficiency is a rare neurometabolic disease due to impaired decarboxylation of neurotransmitter precursors to its active form. Case: We retrospectively reviewed 8 cases from 2008 to 2019 with cerebrospinal fluid neurotransmitter analysis performed at our centre. All cases had an elevated urine vanillactic acid and, in most cases, with N-acetylvanilalanine detected. Cerebrospinal fluid analysis showed low downstream metabolites vanillylmandelic acid, homovanillic acid but high 3-O-methyl-L-DOPA, 5-hydroxytryptophan. Cerebrospinal fluid pterins were normal. Genotyping in DDC confirms the diagnosis. Urine organic acid analysis provided the first clue to diagnosis in four of the cases, which then triggered cerebrospinal fluid neurotransmitter and genetic analysis. We also developed a diagnostic decision support system to assist the interpretation of the mass spectrometry data from urine organic acids. Conclusions Urine organic acid could be essential in guiding subsequent investigations for the diagnosis of aromatic L-amino acid decarboxylase deficiency. We propose to screen suspected cases first with urine organic acids, specifically looking for vanillactic acid and N-acetylvanilalanine. Suggestive findings should be followed with target analysis for c.714 + 4A > T in ethnically Chinese patients. The assistive tool allowed expedite interpretation of profile data generated from urine organic acids analysis. It may also reduce interpreter’s bias when peaks of interest are minor peaks in the spectrum.

Mass spectrometry (MS) is a sensitive, specific and versatile analytical technique in the clinical laboratory that has recently undergone rapid development. From initial use in metabolic profiling, it has matured into applications including clinical toxicology assays, target hormone and metabolite quantitation, and more recently, rapid microbial identification and antimicrobial resistance detection by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In this mini-review, we first succinctly outline the basics of clinical mass spectrometry. Examples of hard ionization (electron ionization) and soft ionization (electrospray ionization, MALDI) are presented to demonstrate their clinical applications. Next, a conceptual discourse on mass selection and determination is presented: quadrupole mass filter, time-of-flight mass spectrometer and the Orbitrap; and MS/MS (tandem-in-space, tandem-in-time and data acquisition), illustrated with clinical examples. Current applications in (1) bacterial and fungal identification, antimicrobial susceptibility testing and phylogenetic classification, (2) general unknown urine toxicology screening and expanded new-born metabolic screening and (3) clinical metabolic profiling by gas chromatography are outlined. Finally, major limitations of MS-based techniques, including the technical challenges of matrix effect and isobaric interference; and novel challenges in the post-genomic era, such as protein molecular variants, are critically discussed from the perspective of service laboratories. Computer technology and structural biology have played important roles in the maturation of this field. MS-based techniques have the potential to replace current analytical techniques, and existing expertise and instrument will undergo rapid evolution. Significant automation and adaptation to regulatory requirements are underway. Mass spectrometry is unleashing its potentials in clinical laboratories.

Superwarfarins are long-acting anticoagulant rodenticides developed from warfarin. The mechanism of action is by inhibition of vitamin K epoxide reductase, resulting in the inability of the body to recycle vitamin K. Deficiency of vitamin K thereafter leads to inability for the body to synthesise vitamin K-dependent coagulation factors, factor II, VII, IX, and X, leading to prolonged prothrombin time. Due to the bulky aromatic sidechains, superwarfarins have a much longer half-life when compared to warfarin, and exposure to superwarfarins results in a prolonged period of anticoagulation which can result in clinical bleeding. Diagnosis is straight forward in patients with known history of superwarfarin exposure but has proved difficult for patients who did not report superwarfarin intake. Superwarfarin poisoning should therefore be suspected in all patients with unexplained prolongation of prothrombin time, and can be confirmed by their detection in serum. Treatment for superwarfarin poisoning includes rapid correction of factor deficiencies with either four factor prothrombin complex concentrate or fresh frozen plasma in patients with active bleeding, and high dose vitamin K therapy given multiple times per day for a prolonged period of weeks to months.

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.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.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.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.

Background It is well known that enzymatic assays for acetaminophen are positively interfered by bilirubin. The effect on acetaminophen not only depends on the concentration of bilirubin but also on that of acetaminophen. We demonstrated a negative interference instead of a positive one in a commonly used routine analyzer and investigated the recovery of acetaminophen in an enzymatic assay by a bi-variate regression. Methods Commercially available blank serum specimens were spiked with acetaminophen and bilirubin at various concentrations, and were analyzed in the Beckman Coulter AU5822 analyzer. The specimens were run in duplicates. The results were then analyzed by least-square analysis and was built into a bi-variate quadratic model. Results The recovery of acetaminophen in this experiment ranged from 38.9% to 100% throughout a range of 23 μmol/L to 2052 μmol/L (for acetaminophen) and 19 μmol/L to 570 μmol/L (for bilirubin). A contour map, as well as a bi-variate equation was established, describing the relationship between acetaminophen recovery, acetaminophen concentration, and bilirubin concentration. Conclusion It was shown that the degree of bilirubin interference in a commercially available acetaminophen assay is dependent on both bilirubin and acetaminophen concentrations. There was a decrease in the apparent acetaminophen concentration by an average of 30% at a bilirubin concentration of 420 μmol/L in the Beckman Coulter AU5822 analyzer. The complex relationship can be modeled by mathematical means. This allows the laboratory staff to estimate the recovery of acetaminophen when bilirubin level is concurrently measured.

Objectives The recent declaration of Ebola virus disease as epidemic by the World Health Organization indicates urgency for affected countries and their laboratories to evaluate and provide treatment to patients potentially infected by the Ebola virus. A heat inactivation procedure involving treating specimens at 60°C for 60 minutes has been suggested for inactivation of the Ebola virus. This study aimed at evaluating the effect of plasma heating on common biochemical tests. Design Comparative experimental study. Setting A regional chemical pathology laboratory in Hong Kong. Methods Forty consecutive plasma specimens for general chemistry analytes on Beckman Coulter AU5822 and another 40 plasma specimens for troponin I analysis on Access 2 Immunoassay System were obtained, anonymised, and divided into two aliquots. One aliquot was analysed directly and the other was analysed after heating at 60°C for 60 minutes. Results A total of 20 chemical pathology tests were evaluated. Nine tests (sodium, potassium, chloride, urea, creatinine, total calcium, phosphate, total protein, and glucose) were not significantly affected by the heat inactivation procedure and remained clinically interpretable. Results for magnesium (15% mean increase), albumin (41% mean increase), bilirubin (8% mean decrease), amylase (27% mean decrease), and troponin I (76% mean decrease) were still interpretable using regression estimation with proportional bias. However, all enzymes studied except amylase (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, and lactate dehydrogenase) were inactivated to a significant degree. Their Pearson r or Spearman rho values ranged from no significant correlation (P≥0.05) to 0.767, and most normality was rejected. Conclusion Heat inactivation results in no significant change in electrolytes, glucose, and renal function tests, but causes a significant bias for many analytes. Recognition of the relationship between pre- and post-heat inactivation specimens allows clinical interpretation of affected values and contributes to patient care. For safety and diagnostic accuracy, we recommend use of a point-of-care device for blood gases, electrolytes, troponin, and liver and renal function tests within a class 2 or above biosafety cabinet with level 3 or above biosafety laboratory practice.

Alpha-dystroglycanopathies are a group of diseases due to reduced glycosylation of alpha-dystroglycan, which commonly result from mutations in POMT1, POMT2, and POMGnT1. Patients with alpha-dystroglycanopathies present with muscular, cerebral, and ocular involvements with differing severities. We reported a boy who presented with muscular dystrophy, developmental delay, and non-specific white matter lesions. Mutation analysis of POMT1 was performed and revealed two novel mutations, a substitution mutation (c.176T>G) and a duplication mutation (c.2059dupC) which results in premature termination of translation. In-silico prediction in five different platforms concurred that the substitution is damaging, and functional studies by immunofluorescence revealed lack of staining in the carbohydrate moiety of alpha-dystroglycan, confirming the molecular findings in a functional manner. In conclusion, we reported the first case of genetically confirmed alpha-dystroglycanopathy due to mutations in POMT1 in Chinese.

This review explores the significance of alpha-2 agonists used clinically in acute pain management.Although alpha-2 agonists have been reported to have an analgesic effect, they are not commonly used clinically for acute pain management. Clinical studies on use of alpha-2 agonists for acute pain management are reviewed and discussed. A literature search was done using Medline with the keywords 'alpha-2 agonist', 'clonidine', 'dexmedetomidine', 'fadolmidine', 'pharmacokinetics', 'pharmacodynamics', 'postoperative analgesia', 'epidural', 'intrathecal', 'peripheral nerve block' and various combinations with these keywords. The years 1977 - 2009 have been included, with particular focus on clinical studies from between 1990 and 2009.This article helps to clarify the clinical use of alpha-2 agonists in acute pain management according to current, up-to-date evidence. Clinically, available alpha-2 agonists, including clonidine and dexmedetomidine, are discussed in detail.Alpha-2 agonists, especially clonidine, seem to be promising with regard to acute postoperative pain management. However, more clinical evidence on dexmedetomidine is necessary to confirm its definite role in acute postoperative pain control.