Multidrug-resistant organism carriage among residents from residential care homes for the elderly in Hong Kong: a prevalence survey with stratified cluster sampling.

INTRODUCTION: A point prevalence survey was conducted to study the epidemiology of and risk factors associated with multidrug-resistant organism carriage among residents in residential care homes for the elderly (RCHEs). METHODS: A total of 20 RCHEs in Hong Kong were selected by stratified single-stage cluster sampling. All consenting residents aged ≥65 years from the selected RCHEs were surveyed by collection of nasal swab, axillary swab, rectal swab or stool on one single day for each home. Specimens were cultured and analysed for methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter (MDRA, defined as concomitant resistant to fluoroquinolones, carbapenems, aminoglycosides, cephalosporins and beta-lactam with or without beta-lactamase inhibitors), vancomycin-resistant Enterococcus (VRE), and carbapenemase-producing Enterobacteriaceae (CPE). One third of the MRSA-positive samples were selected at random for molecular typing; all positive MDRA, VRE and CPE samples were tested for molecular typing. Demographic and health information of residents including medical history, history of hospitalisation, antimicrobial usage, and use of indwelling catheters were collected to determine any associated risk factors. RESULTS: Samples of 1028 residents from 20 RCHEs were collected. Prevalence of MRSA was estimated as 30.1% (95% confidence interval [CI]=25.1%-35.6%) and MDRA 0.6% (95% CI=0.1%-4.1%). No residents carried VRE nor CPE. Residents living in privately run RCHEs were associated with MRSA carriage. Non-Chinese residents were associated with MRSA carriage with borderline significance. CONCLUSIONS: This survey provided information about multidrug-resistant organism carriage among RCHE residents. This information will enable us to formulate targeted surveillance and control strategies for multidrug-resistant organisms.

Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome: a treatable genetic liver disease warranting urgent diagnosis.

Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is an autosomal recessive disorder caused by a defect in ornithine translocase. This condition leads to variable clinical presentations, including episodic hyperammonaemia, hepatic derangement, and chronic neurological manifestations. Fewer than 100 affected patients have been reported worldwide. Here we report the first two cases in Hong Kong Chinese, who were compound heterozygous siblings for c.535C>T (p.Arg179*) and c.815C>T (p.Thr272Ile) in the SLC25A15 gene. When the mother refused prenatal diagnosis for the second pregnancy, urgent genetic testing provided the definitive diagnosis within 24 hours to enable specific treatment. Optimal management of these two patients relied on the concerted efforts of a multidisciplinary team and illustrates the importance of an expanded newborn screening service for early detection and treatment of inherited metabolic diseases.

A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant.

We report an uncommon mitochondrial variant in a baby girl with congenital hyperlactataemia and Leigh syndrome. The patient presented with a single episode of generalised clonic convulsion at day 19, and was found to have isolated and persistent hyperlactataemia ranging from 3.34 to 9.26 mmol/L. She had elevated serum lactate-to-pyruvate ratios of up to 35 and high plasma alanine concentration, indicative of a respiratory chain defect. At the age of 8 months, she developed evolving neurological and imaging features compatible with Leigh syndrome. Genetic testing for common mitochondrial DNA mutations, large mitochondrial DNA deletions, and selected nuclear genes was negative. Further analysis of lymphocyte mitochondrial DNA by sequencing revealed an uncommon heteroplasmic variant, NC_012920.1(MT-ND5):m.13094T>C (p.Val253Ala), which was previously shown to reduce complex I activity. In patients in whom there was a high suspicion of mitochondrial disorder, entire mitochondrial DNA analysis may be warranted if initial screening of common mitochondrial DNA mutations is negative.

A novel mitochondrial DNA deletion in a Chinese girl with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is a rare disorder often caused by mitochondrial DNA rearrangement. The most commonly reported mitochondrial DNA deletion is 4977 bp in size spanning nucleotides 8469 and 13447. The clinical signs of Kearns-Sayre syndrome include chronic progressive external ophthalmoplegia, retinitis pigmentosa, heart block and cerebellar ataxia, as well as other heterogeneous manifestations including neuromuscular problems and endocrine disorders. Cardiac conduction defects can develop insidiously, leading to sudden death sometimes if not promptly recognised. This report focuses on the diagnosis of Kearns-Sayre syndrome in a Chinese girl who presented initially with short stature, delayed puberty, insidious onset of ptosis and later with typical features of Kearns-Sayre syndrome including complete heart block. Genetic analysis disclosed a novel 7.2 kilobases deletion in muscle tissue. Mitochondrial diseases have heterogeneous phenotypes and mutational analysis has proven to be an effective tool for confirming the diagnosis.

Spinocerebellar ataxia type 6.

We report a 39-year-old woman with spinocerebellar ataxia type 6. She presented with ataxia and a 3-year history of progressive ataxia and recurrent falls. There was no relevant family history. Genetic tests revealed an expanded allele of 24 CAG repeats at the spinocerebellar ataxia type 6 locus. This appears to be the first case reported in Hong Kong. As genetic testing becomes more widely available and clinical awareness increases, more such patients are expected to be diagnosed.

Clinical features of hereditary spinocerebellar ataxia diagnosed by molecular genetic analysis.

OBJECTIVE: To assess the frequency and clinical features of different types of hereditary spinocerebellar ataxia in Hong Kong. DESIGN: Cross-sectional study using a questionnaire and clinical examination, with the majority of the information retrospectively collected. SETTING: Three regional hospitals, Hong Kong. PARTICIPANTS: All patients with spinocerebellar ataxia that was confirmed by molecular genetic tests between January 2001 and October 2003. MAIN OUTCOME MEASURES: History, latest physical examination results, clinical investigation results, and genetic profiles. RESULTS: A total of 16 Chinese patients had received diagnoses of spinocerebellar ataxia. These patients had spinocerebellar ataxia type 1 (n=3), spinocerebellar ataxia type 3 (Machado-Joseph disease; n=12), and dentatorubro-pallidoluysian atrophy (n=1). The most common manifestation was ataxia (15/16), followed by pyramidal signs (12/16). Other features such as bulbar dysfunction, ophthalmoplegia, neuropathy, and cognitive impairment were present but variable. CONCLUSIONS: The clinical manifestations of different types of spinocerebellar ataxia overlap, and genetic study is necessary to confirm the diagnosis. The frequency of spinocerebellar ataxia type 3 is greater than that of other types among these Chinese patients. The age of onset of this type may correlate inversely with the number of CAG repeats.

Sitosterolaemia and xanthomatosis in a child.

A 4-year-old boy presented with multiple tuberous xanthomata and a fasting plasma sterol concentration of 18.3 mmol/L, consisting primarily of cholesterol. Two months after changing from an unrestricted diet to a cholesterol-lowering diet, the plasma sterol concentration decreased to 4 mmol/L. Fasting plasma cholesterol levels for his father and mother were 7.3 mmol/L and 6.0 mmol/L, respectively. The degree and rapidity of the child's response to dietary control, together with the fasting cholesterol results of both parents suggested a diagnosis of sitosterolaemia. Gas chromatography and mass spectrometry of the patient's plasma sterol levels showed that the percentage of beta-sitosterol was raised at 12.76%, as was campesterol (6.26%), and stigmasterol (0.71%), confirming the diagnosis of sitosterolaemia. The addition of cholestyramine 4 g/day to a low sterol diet maintained the plasma sterol concentration at 4 to 5 mmol/L, and gradual regression of the xanthoma was observed. These findings indicate that a diagnosis of sitosterolaemia, a treatable cause of premature atherosclerosis, should be considered in children with severe hypercholesterolaemia whose plasma cholesterol level is highly responsive to dietary manipulation.

Kennedy's disease.

Kennedy's disease is an X-linked, neurodegenerative disorder, characterised by lower motor neuron syndrome. This report gives the clinical details of six male patients with Kennedy's disease diagnosed at Princess Margaret Hospital. Three were initially diagnosed with other neurological diseases, with the diagnosis of Kennedy's disease made after genetic testing. This hereditary disease should be considered in male patients with muscle weakness, particularly those with a presentation suggesting atypical motor neuron disease.

Macroprolactin-a cause of pseudohyperprolactinaemia.

Macroprolactin is a complex of immunoglobulin G and monomeric prolactin with little biological activity in vivo. Macroprolactin cross-reacts in modern commercial prolactin assays, however, leading to pseudohyperprolactinaemia. This report is of three patients with macroprolactinaemia and the untoward consequences if this benign condition is misdiagnosed as genuine hyperprolactinaemia are discussed. One adult and one child without symptoms of hyperprolactinaemia were incidentally found to have elevated serum prolactin levels, one of whom had a pituitary incidentaloma. Repeat prolactin measurement after polyethylene glycol precipitation showed that the majority of circulating prolactin was macroprolactin. The third patient had galactorrhoea and pituitary microadenoma. Polyethylene glycol study showed that macroprolactinaemia exists simultaneously with genuine hyperprolactinaemia leading to falsely high serum prolactin levels. The recognition of this relatively common and benign condition is important in order to avoid misdiagnosis and unnecessary investigations and treatment. Particular attention must be paid to patients in whom the clinical and radiological findings are incompatible.

Diagnosis of dihydropyrimidine dehydrogenase deficiency in a neonate with thymine-uraciluria.

Dihydropyrimidine dehydrogenase deficiency is an inborn error of pyrimidine metabolism characterised by thymine-uraciluria, convulsive disorders and developmental delay in paediatric patients, and an increased risk of toxicity from 5-fluorouracil treatment. This report is of the first patient with dihydropyrimidine dehydrogenase deficiency diagnosed in Hong Kong. The patient was a 2-day-old male neonate of Pakistani origin who presented with convulsions. Diagnosis was made by gas chromatographic-mass spectrometric detection of thymine-uraciluria and by molecular detection of a G to A point mutation in a 5'-splicing site leading to skipping of exon 14 in the DPYD gene of chromosome location 1q22. The results showed that the patient and his mother were homozygous and the father heterozygous for the splice site mutation. The mother also had thymine-uraciluria but was clinically asymptomatic.

Mutation screening for tyrosinaemia type I.

This study reports the development of a mutation screening strategy for tyrosinaemia type I, and the identification of six novel mutations in the FAA gene.

Uniform solid-phase extraction procedure for toxicological drug screening in serum and urine by HPLC with photodiode-array detection.

In this HPLC-diode-array detection method for toxicological drug screening, a mixed-mode solid-phase extraction procedure is optimized for isolation of a broad range of drugs from serum and urine. Basic, neutral, and weakly acidic drugs are uniformly recovered. The extract from the solid-phase cartridge is readily injected to a reversed-phase HPLC column for separation by gradient elution. Unknown drugs and metabolites in urine and serum samples from acute drug poisoning cases are rapidly identified by matching their retention times and ultraviolet spectra with hundreds of reference compounds in the library. Urine metabolites of common toxicants from various medications and drugs of abuse are recorded, with their changes of retention times and ultraviolet spectra as related to their metabolic transformations. Glucuronide conjugates of common benzodiazepines, tricyclic antidepressants, and beta-blockers are examined directly without chemical or enzymatic hydrolysis. The system is reliable for diverse clinical investigations of drug overdoses, drug-induced psychoses, and substance abuse.

Nephrogenous cyclic AMP in primary hepatocellular carcinoma patients with or without hypercalcaemia.

OBJECTIVE: To study the relationship between the excretion of nephrogenous cyclic AMP (NcAMP) and other blood and urine parameters as an index of PTH-like activity in patients with primary hepatocellular carcinoma. DESIGN: After overnight fast, a double voided urine and a blood sample were collected from each subject for determination of various analytes and results compared between various groups. PATIENTS: Fifty-five consecutive untreated patients with primary hepatocellular carcinoma, 14 healthy controls and eight patients with cirrhosis only. MEASUREMENTS: Serum calcium, phosphate, alkaline phosphatase, albumin, creatinine and urinary calcium, creatinine and hydroxyproline were measured by routine methods. cAMP was measured in plasma and urine by a radioimmunoassay (Diagnostic Products Corporation) and PTH measured in serum by an immunoradiometric assay (Nichols Institute). TmP/GFR, NcAMP etc. were calculated according to various published methods. RESULTS: Four out of 55 patients (7%) with primary hepatocellular carcinoma had hypercalcaemia. These four patients had significantly lower (P less than 0.05) phosphate, PTH and TmP/GFR and elevated NcAMP (P less than 0.001) compared with normocalcaemic hepatocellular carcinoma and cirrhotic patients, and healthy controls. The excretion of hydroxyproline and calcium was significantly elevated (P less than 0.001) in the hypercalcaemic patients. Bone resorption was found to be the major cause of hypercalcaemia in three of the four hypercalcaemic patients. Fifteen hepatocellular carcinoma patients (29%) with normocalcaemia had suppressed PTH. CONCLUSION: We conclude that a PTH-like humoral factor such as PTH related peptide is the cause of hypercalcaemia in patients with primary hepatocellular carcinoma, and that in some normocalcaemic patients with this tumour PTH is suppressed.