Publications by authors named "Chi Chung Shek"

26 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 Dec 25;53(7):867-874. Epub 2021 May 25.

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
December 2021

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

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

Independent association of serum vitamin D with anti-Mullerian hormone levels in women with polycystic ovary syndrome.

Clin Endocrinol (Oxf) 2018 11 7;89(5):634-641. Epub 2018 Aug 7.

Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.

Objective: This study aimed at investigating the association of serum vitamin D (25(OH)D) and anti-Mullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) as well as non-PCOS healthy ovulatory women and the possible confounding effects of adiposity and androgen.

Method: This was a cross-sectional study conducted on serum samples collected from 451 women diagnosed with PCOS as well as 244 age-matched healthy ovulatory women in a tertiary gynaecology out-patient clinic and a family planning clinic.

Results: Serum 25(OH)D level was significantly higher in women recruited during summer and autumn than those recruited in winter and spring. Both serum 25(OH)D and AMH levels peaked during summer in women with PCOS. In ovulatory women, only serum 25(OH)D but not AMH level showed such seasonal variation. Serum 25(OH)D level in women with PCOS significantly correlated positively with AMH, AMH/antral follicle count (AFC) ratio, serum total testosterone, sex-hormone-binding globulin and quantitative insulin-sensitivity check index and inversely with body mass index (BMI), insulin, triglycerides and homeostatic model assessment of insulin resistance. After controlling for BMI, 25(OH)D level remained significantly correlated positively with serum AMH, AMH/AFC and total testosterone, and inversely with triglycerides. 25(OH)D level was an independent predictor of serum AMH level after controlling for age, BMI and free androgen index in women with PCOS.

Conclusion: Serum 25(OH)D level is an independent factor significantly associated with AMH level in women with PCOS but not in ovulatory women.
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http://dx.doi.org/10.1111/cen.13816DOI Listing
November 2018

Salivary Cortisol and Cortisone After Low-Dose Corticotropin Stimulation in the Diagnosis of Adrenal Insufficiency.

J Endocr Soc 2017 Feb 13;1(2):96-108. Epub 2017 Jan 13.

Department of Medicine and.

Context: Basal and poststimulation salivary cortisol and cortisone levels can be useful in the diagnosis of adrenal insufficiency. However, little is known about the optimal cutoffs and performance characteristics of these tests.

Objective: To derive the cutoff values and study the performance characteristics of salivary cortisol and salivary cortisone in the diagnosis of adrenal insufficiency.

Design And Setting: Prospective study in a regional hospital in Hong Kong from January 2014 to September 2015.

Participants: Fifty-six Chinese healthy volunteers and 171 patients suspected of having adrenal insufficiency.

Main Outcome Measures: All participants underwent low-dose short Synacthen test (LDSST) with intravenous injection of 1 μg of tetracosactide (Synacthen 1-24). Serum cortisol, salivary cortisol and cortisone levels were measured at baseline and 30 and 60 minutes afterward.

Results: Using the reference cutoff (mean - 2 standard deviations of post-LDSST peak serum cortisol) derived from healthy volunteers as the gold standard, receiver operating characteristic analysis of patients' data revealed that both post-LDSST peak salivary cortisol and cortisone performed better than basal tests. The most optimal cutoff values for serum cortisol as measured by immunoassay and for salivary cortisol and salivary cortisone as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were 376, 8.6, and 33.5 nmol/L, respectively, for post-LDSST peak values, and 170, 1.7, and 12.5 nmol/L, respectively, for basal values.

Conclusions: We established method-specific reference cutoffs for serum cortisol, salivary cortisol, and salivary cortisone during LDSST. Both post-LDSST peak salivary cortisol and cortisone performed well as diagnostic tests for adrenal insufficiency. Their measurements by LC-MS/MS can alleviate problems associated with serum cortisol immunoassays.
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http://dx.doi.org/10.1210/js.2016-1056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686556PMC
February 2017

One amino acid makes a difference-Characterization of a new TPMT allele and the influence of SAM on TPMT stability.

Sci Rep 2017 05 2;7:46428. Epub 2017 May 2.

Division of Drug Research, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.

Thiopurine induced toxicity is associated with defects in the thiopurine methyltransferase (TPMT) gene. TPMT is a polymorphic enzyme, with most of the single nucleotide polymorphisms (SNPs) causing an amino acid change, altering the enzymatic activity of the TPMT protein. In this study, we characterize a novel patient allele c.719A > C, named TPMT*41, together with the more common variant *3C c.719A > G, resulting in an amino acid shift at tyrosine 240 to serine, p.Y240S and cysteine, p.Y240C respectively. We show that the patient heterozygote for c.719A > C has intermediate enzymatic activity in red blood cells. Furthermore, in vitro studies, using recombinant protein, show that TPMT p.Y240S is less stable than both TPMTwt and TPMT p.Y240C. The addition of SAM increases the stability and, in agreement with Isothermal Titration Calorimetry (ITC) data, higher molar excess of SAM is needed in order to stabilize TPMT p.Y240C and TPMT p.Y240S compared to TPMTwt. Molecular dynamics simulations show that the loss of interactions is most severe for Y240S, which agrees with the thermal stability of the mutations. In conclusion, our study shows that SAM increases the stability of TPMT and that changing only one amino acid can have a dramatic effect on TPMT stability and activity.
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http://dx.doi.org/10.1038/srep46428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411961PMC
May 2017

Long-term outcome of kidney transplantation in a patient with coexisting lipoprotein glomerulopathy and fibrillary glomerulonephritis.

Clin Kidney J 2014 Aug 17;7(4):396-8. Epub 2014 Jun 17.

Department of Medicine , Queen Elizabeth Hospital , Hong Kong.

Both lipoprotein glomerulopathy (LPG) and fibrillary glomerulonephritis (FGN) are rare causes of end-stage renal disease (ESRD), and the literature concerning the outcome of kidney transplant in patients with LPG or FGN is scarce. We report a patient who suffered from ESRD with coexisting FGN and LPG and received deceased kidney transplant >10 years ago did not reveal any clinical features of disease recurrence during follow-up. Our case shows that the prognosis of patients with LPG component who received kidney transplant can be good. Kidney transplantation remains a viable therapeutic option for patients with ESRD secondary to FGN with LPG.
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http://dx.doi.org/10.1093/ckj/sfu058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377804PMC
August 2014

Diagnosis of 5α-reductase 2 deficiency: is measurement of dihydrotestosterone essential?

Clin Chem 2013 May 19;59(5):798-806. Epub 2013 Mar 19.

Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong SAR.

Background: 5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD.

Methods: We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years.

Results: Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically.

Conclusions: 5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.
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http://dx.doi.org/10.1373/clinchem.2012.196501DOI Listing
May 2013

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

J Pediatr Endocrinol Metab 2011 ;24(3-4):193-6

Department of Pediatrics and Adolescent Medicine, Tuen Mun Hospital, New Territories, Hong Kong, PR China.

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.
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http://dx.doi.org/10.1515/jpem.2011.090DOI Listing
July 2011

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

Development of a broad toxicological screening technique for urine using ultra-performance liquid chromatography and time-of-flight mass spectrometry.

Anal Chim Acta 2009 Sep 28;649(1):80-90. Epub 2009 Jul 28.

Department of Clinical Pathology, Tuen Mun Hospital, Tuen Mun, Hong Kong.

Withdrawal of the support for the REMEDi HS drug profiling system has necessitated its replacement within our laboratories with an alternative broad toxicological screening technique. To this end, a novel method, based on ultra-performance liquid chromatography (UPLC) and time-of-flight (TOF) mass spectrometry, was developed for the routine analysis of urine samples. Identification was achieved by comparison of acquired data to libraries containing more than 300 common drugs and metabolites, and was based on a combination of retention time, exact mass and fragmentation patterns. Validation data for the method is presented and comprised an evaluation of the following parameters: precision; transferability of the methodology between the six collaborating laboratories; specificity; extraction recovery and stability of processed samples; matrix effects and sensitivity. This paper presents the benefits of supplementary fragmentation data with particular regard to increasing specificity and confidence of identification and its usefulness with overdosed samples. The utility of the method was assessed by the parallel analysis of 30 authentic urine samples using the REMEDi HS and UPLC-TOF. The latter provided enhanced detection, leading to the identification of twice as many drugs. Furthermore it did not miss any compounds that were identified by REMEDi HS. The UPLC-TOF findings were further verified by a combination of data from three other conventional screening techniques, i.e., GC-MS, HPLC-DAD and UPLC-MS/MS.
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http://dx.doi.org/10.1016/j.aca.2009.06.068DOI Listing
September 2009

Homocysteine level in schizophrenia patients.

Aust N Z J Psychiatry 2009 Aug;43(8):760-5

Department of Psychiatry, Kowloon Hospital, Kowloon, Hong Kong.

Objective: Elevated serum levels of homocysteine have been shown to be associated with schizophrenia in some studies, but the evidence is still limited and mixed. The aim of the present study was therefore to evaluate the serum homocysteine level in Chinese in schizophrenia patients and assess its association with clinical phenotypes of the disease.

Method: A total of 250 inpatients and 250 healthy controls were identified at Kowloon Hospital and the Red Cross Blood Donation Centre, respectively. Each subject was evaluated with a structured diagnostic interview. Demographic data were collected and blood was analysed for homocysteine level. The Positive and Negative Syndrome Scale was used to grade clinical symptoms of schizophrenia. Confounding factors affecting homocysteine levels were controlled by strict exclusion criteria or statistical methods.

Results: Serum homocysteine level was elevated in Chinese schizophrenia patients. Both male (mean, 12.26 micromol L(-1); control, 11.40 micromol L(-1), p = 0.026) and female (mean, 9.61 micromol L(-1); control, 8.33 micromol L(-1), p < 0.001) patients had a higher serum homocysteine level than the healthy controls, and these differences persisted after controlling for age. There was no significant association between serum homocysteine level and duration of illness, clinical symptoms or age of onset of schizophrenia.

Conclusion: The serum homocysteine levels were elevated in both male and female Chinese schizophrenia patients. The levels were not apparently related to other clinical parameters.
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http://dx.doi.org/10.1080/00048670903001935DOI Listing
August 2009

Can daclizumab reduce acute rejection and improve long-term renal function in tacrolimus-based primary renal transplant recipients?

Nephrology (Carlton) 2008 Jun 23;13(3):251-5. Epub 2008 Jan 23.

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

Aims: To evaluate the efficacy and safety of a tacrolimus-based immunosuppressive regimen with and without induction therapy using daclizumab in first cadaveric renal transplant recipients.

Methods: Since January 2001, we studied the effect of daclizumab in a non-randomized and prospective study of 36 sequential first cadaveric renal transplant recipients. They were compared with a historical control group of 21 sequential first cadaveric renal transplant recipients without induction therapy. All patients received tacrolimus, azathioprine and corticosteroids as concomitant immunosuppressive therapy. Daclizumab was given at 1 mg/kg infusion 2 h before transplantation and then every 14 days for four more doses. Outcomes measured included incidence of acute rejection, patient survival, graft survival, annualized change in creatinine clearance (CrCl), cardiovascular risk profile, infection and malignancy.

Results: Fewer biopsy proven acute rejections were observed in the induction treatment group: 11.1% (4/36) versus 19% (4/21) but the rejection free survival was similar (P = 0.37). The patient survival and graft survival were comparable. The renal function was similar in both groups. There were also no significant difference in infection, malignancy and cardiovascular risk profile in both groups.

Conclusion: Adding daclizumab to a tacrolimus-based therapy is safe but cannot further improve clinical efficacy.
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http://dx.doi.org/10.1111/j.1440-1797.2007.00911.xDOI Listing
June 2008

Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation.

Transpl Int 2008 Feb 17;21(2):140-5. Epub 2007 Oct 17.

Renal Unit, Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China.

Dried blood spot (DBS) sampling and high-performance liquid chromatography tandem-mass spectrometry have been developed in monitoring tacrolimus levels. Our center favors the use of limited sampling strategy and abbreviated formula to estimate the area under concentration-time curve (AUC(0-12)). However, it is inconvenient for patients because they have to wait in the center for blood sampling. We investigated the application of DBS method in tacrolimus level monitoring using limited sampling strategy and abbreviated AUC estimation approach. Duplicate venous samples were obtained at each time point (C(0), C(2), and C(4)). To determine the stability of blood samples, one venous sample was sent to our laboratory immediately. The other duplicate venous samples, together with simultaneous fingerprick blood samples, were sent to the University of Maastricht in the Netherlands. Thirty six patients were recruited and 108 sets of blood samples were collected. There was a highly significant relationship between AUC(0-12), estimated from venous blood samples, and fingerprick blood samples (r(2) = 0.96, P < 0.0001). Moreover, there was an excellent correlation between whole blood venous tacrolimus levels in the two centers (r(2) = 0.97; P < 0.0001). The blood samples were stable after long-distance transport. DBS sampling can be used in centers using limited sampling and abbreviated AUC(0-12) strategy as drug monitoring.
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http://dx.doi.org/10.1111/j.1432-2277.2007.00584.xDOI Listing
February 2008

Health-related quality-of-life study in patients with carcinoma of the thyroid after thyroxine withdrawal for whole body scanning.

Laryngoscope 2006 Nov;116(11):2060-6

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China.

Objectives/hypothesis: The authors studied the change of health-related quality of life (HR-QOL) in patients with differentiated thyroid carcinoma (DTC) with thyroxine (T4) withdrawal in preparation for whole body radioactive iodine scanning.

Study Design: Seventy-eight patients with DTC and history of radioactive iodine (RAI) ablation were prospectively recruited. They completed the Functional Assessment of Cancer Treatment-General (FACT-G) questionnaire on weeks 0, 2, and 4 after T4 withdrawal with corresponding checking of serum thyroid-stimulating hormone (TSH).

Results: Overall, 74.5% (58 of 78) of patients completed all FACT-G. Comparing FACT-G scores at weeks 0 and 4, "physical" (P < .001), "social" (P = .04), and "emotional" (P = .047) aspects were lowered as well as "total" HR-QOL (P = .001). However, the "functional" domain of HR-QOL was not affected (P = .14). Comparing FACT-G scores at week 0 and 2, we found that "physical" (P = .049) and "total" (P = .05) HR-QOL were affected early (in the first 2 weeks) in T4 withdrawal. Comparison of week 2 and 4 showed that in the later half of the withdrawal period, "physical" (P = .001), "emotional" (P = .02), and "total" FACT-G scores (P = .002) were affected. Mean TSH level (in mIU/L) increased gradually: 2.8 (week 0), 42.8 (week 2), 97 (week 3), and 153 (week 4). The percentage of patients attaining TSH level of >30 mIU/L were 55% (week 2), 96.2% (week 3), and 100% (week 4).

Conclusions: HR-QOL declines with time of T4 withdrawal. The impact is more severe in the later period of T4 withdrawal. In 3 weeks, 96.2% of our patients attained TSH level of 30 mIU/L. To minimize the impact on HR-QOL, duration of T4 withdrawal can be decreased to 3 weeks.
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http://dx.doi.org/10.1097/01.mlg.0000240287.57704.01DOI Listing
November 2006

A novel nonsense mutation in the LPL gene in a Chinese neonate with hypertriglyceridemia.

Clin Chim Acta 2006 Jun 7;368(1-2):120-4. Epub 2006 Feb 7.

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

Background: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder characterized by hypertriglyceridemia. The genetic defect lies in a mutation of the LPL gene.

Methods: A Chinese neonate with non-consanguineous parents was incidentally found to have hypertriglyceridemia. Mutation in her LPL gene was screened by using polymerase chain reaction and direct DNA sequencing.

Results: Homozygous missense mutations (L252V) were detected in the LPL gene of the patient. A novel nonsense mutation (C27X) was also identified.

Conclusion: Our finding supports L252V mutation in the LPL gene is a common mutation in Chinese with familial hyperchylomicronemia syndrome. DNA-based diagnosis in this syndrome is definitive. It saves the need for heparin-infusion test, which carries the risk of hemorrhage, and the measurement of LPL activity, which is tedious and is not widely available.
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http://dx.doi.org/10.1016/j.cca.2005.12.020DOI Listing
June 2006

DNA-based diagnosis of thyroid hormone resistance syndrome: a novel THRB mutation associated with mild resistance to thyroid hormone.

Clin Chim Acta 2005 Aug;358(1-2):55-9

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Background: Thyroid hormones govern a wide range of metabolic processes in the body via thyroid hormone receptors (TR). We report a patient with mild resistance to thyroid hormone who was initially misdiagnosed and treated as having thyrotoxicosis.

Methods: We used direct DNA sequencing of the THRB gene.

Results: We identified a novel missense mutation, I276L, located in exon 8 of the gene. The mutation is located in cluster 3 of the ligand-binding domain, a protein domain associated with resistance to thyroid hormone.

Conclusion: DNA-based diagnosis of thyroid hormone resistance syndrome is simple, reliable, and economical compared to traditional biochemical tests. Once the mutation is identified, targeted screening for the whole family can be performed and the unnecessary use of anti-thyroid drugs or thyroidectomy can be avoided.
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http://dx.doi.org/10.1016/j.cccn.2005.02.014DOI Listing
August 2005

A novel mutation, Y255X, of the ARSB gene in a Chinese family with mucopolysaccharidosis type VI.

Chin Med J (Engl) 2004 Dec;117(12):1850-2

Department of Chemical Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China.

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December 2004

Novel mutations in the BCHE gene in patients with no butyrylcholinesterase activity.

Clin Chim Acta 2005 Jan;351(1-2):155-9

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

Background: Butyrylcholinesterase (BCHE) deficiency is characterized by prolonged apnea after the use of certain muscle relaxants with the genetic defect lying in the BCHE gene.

Methods: Two Chinese patients with no serum BCHE activity were studied. The BCHE genes were screened for mutations by polymerase chain reaction and direct DNA sequencing.

Results: Of the four mutations detected, two novel mutations were identified in the two patients, i.e., F474L, and an insertion of an adenine between nucleotide positions 395 and 396. This information was used to screen the immediate families of the patients for carrier status.

Conclusions: We established the molecular basis of butyrylcholinesterase deficiency in two Chinese patients. The developed mutation detection assay provides a reliable method for identifying mutant BCHE carriers.
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http://dx.doi.org/10.1016/j.cccn.2004.09.004DOI Listing
January 2005

The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling.

J Clin Endocrinol Metab 2005 Jan 13;90(1):72-8. Epub 2004 Oct 13.

Department of Medicine, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong Special Administrative Region, China.

Recent reviews recommended the use of the aldosterone/renin ratio (ARR) to screen for primary hyperaldosteronism. However, widely different cutoff levels have been proposed, and test characteristics of ARR under different conditions of sampling are not known. We conducted a retrospective review among 45 subjects with carefully validated diagnoses of primary hyperaldosteronism and 17 subjects with essential hypertension to study the utility of ARR. Sixty-two patients with 75 sets of plasma renin activity (PRA), aldosterone, and ARR values from a postural study and 48 sets of values from a saline suppression test were analyzed. Ninety-four percent of these subjects underwent investigations because of hypokalemic hypertension.ARR yielded larger areas under the curve in the receiver-operating-characteristics curve than PRA or aldosterone under all conditions of testing. Our results confirmed the superiority of ARR to either aldosterone or PRA alone as a diagnostic test for primary hyperaldosteronism.ARR cutoff levels were significantly affected by the condition of testing. Depending on posture and time of day, it varied from 13.1-35.0 ng/dl per ng/ml.h in our study population. When using ARR for screening primary hyperaldosteronism, posture and time of sampling should be standardized both within and between centers to minimize variability in cutoff levels.
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http://dx.doi.org/10.1210/jc.2004-1149DOI Listing
January 2005

Steroid 5alpha-reductase 2 deficiency in two generations of a non-consanguineous Chinese family.

J Pediatr Endocrinol Metab 2003 Oct-Nov;16(8):1197-201

Department of Paediatrics, Caritas Medical Centre, Hong Kong, China.

We report a Chinese family in which two family members were diagnosed to have steroid 5alpha-reductase 2 deficiency. The proband was an 8 year-old boy presenting with isolated micropenis. Mutational analysis revealed a homozygous mutation in exon 4 of the SRD5A2 gene, changing codon 227 from CGA to CAA, i.e. R227Q. The paternal granduncle of the proband has incomplete virilization in adulthood. Besides having the mutation R227Q, he has another mutation in exon 5 of the SRD5A2 gene, changing codon 246 from CGG to CAG, i.e. R246Q. To our knowledge, this is the first reported Chinese family diagnosed with steroid 5alpha-reductase 2 deficiency with identified molecular defects.
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November 2004

Increased bone mineral density in patients with chronic hypoparathyroidism.

J Clin Endocrinol Metab 2003 Jul;88(7):3155-9

Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China.

Bone mineral density (BMD) has been shown to be increased in postmenopausal females with postthyroidectomy hypoparathyroidism, but it is not known whether similar gains occur in patients with idiopathic hypoparathyroidism. In this study, we measured the BMD of lumbar spine and proximal femur in 14 patients, 8 with idiopathic hypoparathyroidism and 6 with postthyroidectomy hypoparathyroidism, using dual-energy x-ray absorptiometry. Their age ranged from 23-57 yr old, with a mean of 42.5 yr. The results showed that patients with hypoparathyroidism had a higher BMD than the normal age- and sex-matched population. This was particularly evident at the lumbar spine (L2-L4), with positive Z-score of 1.93 +/- 1.03, whereas Z-score at the femoral neck was 1.14 +/- 0.62 SD. Subgroup analysis showed that those with postthyroidectomy hypoparathyroidism had a mean lumbar spine BMD of 1.434 g/cm(2) and femoral neck BMD of 1.026 g/cm(2), compared with a mean BMD of 1.364 g/cm(2) and 1.022 g/cm(2) at spine and hip, respectively, for those with idiopathic hypoparathyroidism. Statistical analysis did not reveal any significant difference in the BMD, T-score, and Z-score of the bone, at these two sites, between the two groups. In conclusion, the state of chronic hypoparathyroidism is associated with increased BMD, especially at the lumbar spine. Those with idiopathic hypoparathyroidism have a similar degree of increase in BMD as those with postthyroidectomy hypoparathyroidism.
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http://dx.doi.org/10.1210/jc.2002-021388DOI Listing
July 2003
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