Anemia, Sideroblastic ; complications ; Bone Marrow Cells ; pathology ; Female ; Humans ; Hydrops Fetalis ; etiology ; Infant, Newborn ; Pancreatic Diseases ; complications

INTRODUCTIONStenotrophomonas maltophilia is an aerobic gram-negative bacillus that is a frequent coloniser of fluids used in the hospital setting. It causes infection in immunosuppressed hosts, especially those who are neutropaenic, on chemotherapy and broad spectrum antibiotics. Skin and soft tissue manifestations of Stenotrophomonas maltophilia infection are becoming an increasingly recognised entity; the clinical spectrum ranges from mucocutaneous, skin to soft tissue infections.

MATERIALS AND METHODSWe present a case of an 8-year-old girl with acute myeloid leukaemia who developed metastatic skin lesions secondary to Stenotrophomonas maltophilia bacteraemia. The authors reviewed a total of 24 reported cases of mucocutaneous, skin and soft tissue infections by Stenotrophomonas maltophilia. The presentations include metastatic cellulitis, primary cellulitis and infected mucocutaneous ulcers.

RESULTSThis is the first locally reported case of metastatic nodular skin lesions caused by Stenotrophomonas maltophilia bacteraemia. This is also the first reported paediatric case of embolic skin lesions caused by Stenotrophomonas maltophilia. Of the 6 cases of Stenotrophomonas maltophilia bacteraemia seen in the paediatric oncology patients from year 2000 to 2004 at our hospital, only 1 case developed metastatic skin lesions.

CONCLUSIONStenotrophomonas maltophilia skin infection should be included into the list of differential diagnoses for metastatic skin lesions in neutropaenic patients, especially with an underlying haematologic malignancy who has received recent chemotherapy and broad spectrum antibiotics. Haematologic malignancy, transplantation, neutropaenic, immunosuppressive therapy and a high severity of illness score were important prognostic factors.

Acute Disease ; Anti-Infective Agents ; therapeutic use ; Bacteremia ; epidemiology ; microbiology ; Cellulitis ; epidemiology ; microbiology ; Child ; Comorbidity ; Female ; Gram-Negative Bacterial Infections ; complications ; Humans ; Leukemia, Myeloid ; epidemiology ; Neutropenia ; epidemiology ; Prognosis ; Skin Diseases, Bacterial ; epidemiology ; Stenotrophomonas maltophilia ; Trimethoprim, Sulfamethoxazole Drug Combination ; therapeutic use

Child ; Female ; Humans ; Male ; Mucopolysaccharidosis IV ; genetics ; Mutation ; N-Acetylgalactosamine-4-Sulfatase ; genetics

Asian Continental Ancestry Group ; genetics ; Carnitine Acyltransferases ; deficiency ; genetics ; China ; Founder Effect ; Humans ; Infant, Newborn ; Male ; Mutation ; Sudden Infant Death ; genetics

BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

BACKGROUNDData 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.

METHODSThe 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.

RESULTSAmong 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.

CONCLUSIONSOur 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.

Acids ; urine ; Amino Acids ; blood ; Carnitine ; analogs & derivatives ; blood ; Hong Kong ; epidemiology ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; blood ; diagnosis ; epidemiology ; urine ; Neonatal Screening ; methods ; Tandem Mass Spectrometry

OBJECTIVETo investigate the role of a potential diabetes-related mitochondrial region, which includes two previously reported mutations, 3243A-->G and 3316G-->A, in Chinese patients with adult-onset type 2 diabetes.

METHODSA total of 277 patients and 241 normal subjects were recruited for the study. Mitochondrial nt 3116 - 3353, which spans the 16S rRNA, tRNA(leu(UUR)) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR-restriction fragment length polymorphism and allele-specific PCR. Variants were analyzed by two-tailed Fisher exact test. The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3.

RESULTSFour homoplasmic nucleotide substitutions were observed, 3200T-->C, 3206C-->T, 3290T-->C and 3316G-->A. Only the 3200T-->C mutation is present in the diabetic population and absent in the control population. No statistically significant associations were found between the other three variants and type 2 diabetes. The 3200T-->C and 3206C-->T nucleotide substitutions located in 16S rRNA are novel variants. The 3200T-->C caused a great alteration in the minimal free energy secondary structure model while the 3206C-->T altered normal 16S rRNA structure little.

CONCLUSIONSThe results suggest that the 3200T-->C mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral. In contrast to the Japanese studies, the 3316G-->A does not appear to be related to type 2 diabetes.

Age of Onset ; Aged ; Alleles ; Base Sequence ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Humans ; Middle Aged ; Models, Molecular ; Nucleic Acid Conformation ; Point Mutation ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S ; chemistry ; genetics

OBJECTIVETo investigate the role of lipoprotein lipase (LPL) gene on Chinese patients with hypertriglyceridemic type 2 diabetes.

METHODSThree subject groups, including hypertriglyceridemic group, normalipidemic type 2 diabetes group and healthy controls, were recruited and screened for sequence changes in LPL gene with PCR, SSCP, restriction analysis and direct DNA sequencing. LPL mass and activity in post-heparin plasma and in in vitro expression were investigated. Comparative modeling was performed via Swiss-PDB Viewer to provide the potential 2-D structures of wildtype and mutant proteins.

RESULTSFour missense mutations, Ala71Thr, Val18Ile, Gly188Glu and Glu242Lys, were identified in patients with hypertriglyceridemic type 2 diabetes, and not in both normalipidemic diabetes and the control subjects. The four missense mutations were located in the highly conserved amino acid sites, which are involved in highly conserved exon 3, 5, or 6 regions. They led to reduced LPL mass and enzyme activities in both post-heparin plasma and in vitro expression. The modeled structures displayed the differences to a great extent between the mutant and wide-type molecules.

CONCLUSIONThese results indicated that the 4 missense mutations lead to LPL deficiency and subsequent hypertriglyceridemia. The LPL deficiency predispose a progressive diabetic pathway to those affected individuals. LPL gene is one of susceptibility gene for hypertriglyceridemic type 2 diabetes.

Asian Continental Ancestry Group ; Diabetes Mellitus, Type 2 ; complications ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Hypertriglyceridemia ; complications ; enzymology ; genetics ; Lipoprotein Lipase ; genetics ; Male ; Middle Aged ; Mutation, Missense ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational

Adolescent ; Death, Sudden, Cardiac ; etiology ; Female ; Humans ; Ion Channels ; physiology ; Mutation ; Ryanodine Receptor Calcium Release Channel ; genetics ; Syncope ; etiology ; Tachycardia, Ventricular ; genetics

Child ; Dystonia Musculorum Deformans ; diagnostic imaging ; drug therapy ; genetics ; Female ; Humans ; Male ; Molecular Chaperones ; genetics ; Mutation ; Pedigree ; Positron-Emission Tomography