Publications by authors named "Mei Tik Leung"

8 Publications

  • Page 1 of 1

Case Report: The first familial hCG syndrome in a Chinese family.

F1000Res 2021 8;10:458. Epub 2021 Jun 8.

Chemical Pathology Laboratory, Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.

Familial hCG syndrome is a rare and benign cause of elevated serum beta human chorionic gonadotropin (hCG). We present here a case of familial hCG syndrome diagnosed in a Hong Kong Chinese family, which we believe to be the first reported in Chinese. A 38-year-old woman presented with incidental finding of persistently elevated hCG, analytically confirmed both in urine and blood. Extensive radiological and biochemical work-up were performed but were negative for pregnancy and malignancy. Testing of another asymptomatic family member revealed unexplained elevation of serum hCG, confirming the diagnosis of familial hCG syndrome. Knowledge and awareness of this entity among clinicians are important to avoid unnecessary investigations and treatment in affected families.
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http://dx.doi.org/10.12688/f1000research.53636.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240598PMC
July 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

Nephrogenic syndrome of inappropriate antidiuresis - An ethnically, genetically and phenotypically diverse disorder: First report in a Chinese adult and review of published cases.

Clin Chim Acta 2021 Aug 11;519:214-219. Epub 2021 May 11.

Department of Pathology, Queen Elizabeth Hospital, Hong Kong.

Background: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare inherited disorder characterised by hyponatraemia. To date, most reported cases are Caucasians with gain-of-function variants in AVPR2, an X-linked gene which encodes the vasopressin V2 receptor (V2R). Recently, germline gain-of-function variants in the stimulatory G protein α-subunit (Gsα) were reported to cause dominantly inherited NSIAD.

Case Report: We report the first Chinese adult diagnosed with NSIAD. He was found to be hemizygous for R137C-V2R, the most prevalent pathogenic variant among Caucasians. After the genetic diagnosis and counselling on the importance of fluid restriction, he had no recurrence of hyponatraemia to date.

Literature Review: Case reports of NSIAD published in the English literature in PubMed were reviewed to summarise the genetic and phenotypic heterogeneity of this disorder.

Conclusion: NSIAD is ethnically, genetically and phenotypically diverse. The diagnosis should especially be considered in young patients with otherwise unexplained hyponatraemia. Target analysis of R137C-V2R should make the diagnosis in most cases. Genetic testing could confirm the diagnosis, motivate adherence to treatment, offer the possibility of genotype-guided therapy, and allow cascade screening to prevent hyponatraemia.
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http://dx.doi.org/10.1016/j.cca.2021.05.006DOI Listing
August 2021

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

Isolated 17,20-Lyase Deficiency in a Mutated Female With Normal Sexual Development and Fertility.

J Endocr Soc 2020 Feb 18;4(2):bvz016. Epub 2019 Nov 18.

Department of Pathology, Queen Elizabeth Hospital, Jordan, Kowloon, Hong Kong.

Isolated 17,20-lyase deficiency may be caused by mutations in the (coding for cytochrome P450c17), (coding for cytochrome P450 oxidoreductase) and (coding for microsomal cytochrome b5) genes. Of these, mutations in the gene have thus far only been described in genetic males who presented with methemoglobinemia and 46,XY disorders of sex development (DSD) due to 17,20-lyase deficiency. A 24-year-old Chinese woman presented to the hematology outpatient clinic with purplish discoloration of fingers, toes, and lips since childhood. Investigations confirmed methemoglobinemia. A homozygous c.105C>G (p.Tyr35Ter) nonsense mutation was detected in the gene. Hormonal studies showed isolated 17,20-lyase deficiency. Interestingly, she had a completely normal female phenotype with no DSD, normal pubertal development, and spontaneous pregnancy giving birth uneventfully to a healthy female infant. The sex hormone-related features of genetic females with 17,20-lyase deficiency due to cytochrome b5 gene mutation appear to differ from that of females with 17,20-lyase deficiency caused by other genetic defects who presented with hypergonadotropic hypogonadism and infertility and differ from genetic males with the same mutation.
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http://dx.doi.org/10.1210/jendso/bvz016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007803PMC
February 2020

Facial Puffiness in a 9-Year-Old Girl.

Clin Chem 2020 04;66(4):627-628

Department of Chemical Pathology, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

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http://dx.doi.org/10.1093/clinchem/hvaa006DOI Listing
April 2020

Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families.

J Pediatr Endocrinol Metab 2019 Aug;32(8):915-920

Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.

Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), resulting in dilute urine and polyuria. Causes of NDI are heterogeneous and diagnosing congenital NDI (cNDI) in young infants is clinically challenging, as typical symptoms are often unappreciated or inconspicuous. Instead, young infants may present with non-specific signs such as vomiting, poor feeding, failure to thrive, unexplained fevers, irritability, constipation or diarrhea. We report a 37-day-old infant who presented with polyuria and severe hypernatremic dehydration that was unresponsive to vasopressin. The patient was treated with amiloride, indomethacin and hydrochlorothiazide. Genetic analysis revealed a novel contiguous deletion involving the entire AVPR2 gene and the last exon of the adjacent ARHGAP4 gene. A study of the family confirmed the carrier status in the mother. This case illustrates the importance of molecular testing in confirming the diagnosis in the index patient, as well as in identifying asymptomatic at-risk female carriers so that appropriate genetic counselling can be given for reproductive planning. All pediatric patients with suspected cNDI should undergo genetic analysis for a definitive diagnosis.
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http://dx.doi.org/10.1515/jpem-2019-0028DOI Listing
August 2019
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