Vietnamese Patient Research Articles

AB126. Enzyme replacement therapy in patient with mucopolysaccharidosis type I: a case report

Background and objective Mucopolysaccharidosis I (MPS I) is a rare, recessively inherited, lysosomal storage disorder caused by deficiency on the enzyme α-L-iduronidase. This defect results in accumulation of heparan and dermatan sulfate in different tissues and organs due to a deficiency in the catabolism of glycosaminoglycans. The overall incidence of MPS I is 0.99-1.99/100,000 live births. Enzyme replacement therapy (ERT) with recombinant α-L-iduronidase (laronidase) has shown to significantl improve the quality of life in children. To describe clinical characteristics, enzyme activity and genetic finding in the first Vietnamese patient with MPS type I with aldurazyme replacement therapy.

Vietnamese patient with progressive ataxia and palatal tremor syndrome

Background: We present clinical and MRI features of progressive ataxia and palatal tremor (PAPT). Case Report: A 67 year-old gentleman visiting from Vietnam presented with intermittent stroke-like episodes consisting of facial weakness, dysarthria, and osillopsia. He reported gradually worsening ataxia and dysequilibrium over 4 years. Examination revealed small amplitude nystagmus towards the right, impaired VOR to the left, palatal tremor, left-sided dysmetria, and an unsteady gait. MRI of the brain demonstrated increased T2/FLAIR signal within the inferior olive. Contrast enhanced and diffusion sequences were normal. MRA was normal. Electrocardiography, telemetry, and echocardiogram were normal. CSF was normal. Glial fibrillary acidic protein (GFAP) and vitamin E levels were normal. Genetic testing for hereditary forms of ataxia including spinocerebellar ataxia was not completed. Conclusion: Palatal tremor is commonly classified into symptomatic or essential subgroups. Symptomatic palatal tremor is frequently caused by a lesion in the triangle of Guillain and Mollaret leading to hypertrophic olivary degeneration. A subgroup of symptomatic palatal tremor form a syndrome of PAPT. Published details of cases of PAPT are sparse and the disorder appears to be mainly sporadic. Common features include progression of ataxia, olivary degeneration, gaze-evoked nystagmus, and internuclear ophthalmoplegia. There is no known effective treatment for progressive ataxia, which is the most disabling symptom of PAPT.

46,XY disorder of sex development and wilms’ tumor due to mutation of WT1 gene: a case report

The Wilms' tumor suppressor gene (WT1) is a transcription factor that plays a major role in development of the gonads and kidneys. It is expressed even earlier than sex-determining region of the Y chromosome in the urogenital ridge from which the gonads and kidneys are derived. WT1 mutations will impair gonadal and urinary tract development and have been demonstrated to cause syndromes of WAGR, Denys–Drash and Fraiser. In this study, our aim is to identify mutation in WT1 gene and to describe clinical features of a Vietnamese patient with 46,XY disorder of sex development (DSD) associated with Wilms’ tumor. DNA was extracted from WBC and mutation analysis of WT1 gene was performed using PCR and direct sequencing. A 5 days newborn presented with penoscrotal hypospadias, microphallus, right testis in the right inguinal and no left testis was found. Karyotype was 46,XY and no ovaries and uterus were found using pelvic ultrasound. Wilms’ tumor was detected at 13 months of age by abdominal ultrasound and CT scan. Mutation analysis was identified a heterozygous missense mutation (c.1390G>A; p.D464N) in exon 9 of WT1 gene. In conclusions, WT1 analysis should be performed in newborns with complex hypospadias with at least one cryptorchid testis and in isolated 46,XY partial to complete gonadal dysgenesis. WT1 analysis is mandatory in all 46,XY DSD with associated kidney disease. Patients with WT1 mutations should be followed up closely because the risk of developing a Wilms' tumor, nephropathy. Written informed consent was obtained from the patient's parent or guardian for publication of this Case report (and any accompanying images). A copy of the written consent is available for review by the Editor-in-Chief of this journal.

A novel homozygous mutation IVS6+5G>T in CYP11B1 gene in a Vietnamese patient with 11β-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. CAH cases arising from impaired 11β-hydroxylase are the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. This study was performed on a patient with congenital adrenal hyperplasia and with premature development such as enlarged penis, muscle development, high blood pressure, and bone age equivalent of 5years old at 2years of chronological age. Biochemical tests for steroids confirmed the diagnosis of CAH. We used PCR and sequencing to screen for mutations in CYP11B1 gene. Results showed that the patient has a novel homozygous mutation of guanine (G) to thymine (T) in intron 6 (IVS6+5G>T). The analysis of this mutation by MaxEntScan boundary software indicated that this mutant could affect the gene splicing during transcription.

Clinical determinants of early parasitological response after ACT treatment in patients diagnosed with uncomplicated malaria in Africa: a pooled analysis of individual patient data

Background Artemisinin resistant P. falciparum malaria has emerged in Western Cambodia and now has been observed in Thailand, Vietnam and Myanmar and Lao. In addition, there is a recent report of a Vietnamese patient, apparently infected with P. falciparum in Angola, who was unresponsive to artemisinin treatment. This makes it even more urgent to have baseline information on early parasite response to ACTs in African patients, the first step in establishing surveillance for this important phenotype.

Co-colonization of vanA and vanB Enterococcus faecium of clonal complex 17 in a patient with bacteremia due to vanA E. faecium

A 53-year-old Vietnamese man with liver cirrhosis was transferred from a Vietnamese hospital to our tertiary care hospital in Korea in order to undergo a liver transplantation. Bacteremia due to vanA Enterococcus faecium was diagnosed, and stool surveillance cultures for vancomycin-resistant enterococci (VRE) were positive for both vanA and vanB E. faecium. Pulsed-field gel electrophoresis analysis revealed that the 2 vanA VRE isolates from the blood and stool were clonal, but the vanB VRE was unrelated to the vanA VRE. vanA and vanB VRE were ST64 and ST18, single-allele variations of clonal complex 17, respectively. This is the first case report of vanA VRE bacteremia in a Vietnamese patient and demonstrates the reemergence of vanB VRE since a single outbreak occurred 15years ago in Korea. The reemergence of vanB VRE emphasizes the importance of VRE genotyping to prevent the spread of new VRE strains.

One to One honors pharmacists, student pharmacists for exceptional counseling

The One to One Patient Counseling Recognition Program, now in its 11th year, acknowledges the inspiring efforts of 20 pharmacists and five student pharmacists committed to providing outstanding patient care. Pharmacy Today and Student Pharmacist honor these individuals for going to great lengths to keep their patients and their communities well.

One to One honors pharmacists, student pharmacists for exceptional counseling

One to One honors pharmacists, student pharmacists for exceptional counseling

Multiple Nail Gun Penetrating Head Injury: A Case Report

Intracranial nail gun injury is a rare subset of penetrating head injury. Here we report a case of intracranial nail gun injury in a Vietnamese patient who attempted suicide with no neurological deficit. Three nails were launched. Because the nail head acted as a brake, the launched nail could make a hole into the skull but could not entirely pass it. A rational management strategy should permit these patients to be discharged with no additional injury. Some medical and surgical management in penetrating head injury are discussed. The use of antibiotics and antiepileptic drugs and the retraction of the nail aided by the performance of a craniotomy surrounding the entry point are recommended.

Novel homozygous p.Y395X mutation in the CYP11B1 gene found in a Vietnamese patient with 11β-hydroxylase deficiency

ContextThe deficiency of steroid 11β-hydroxylase is caused by mutations in the CYP11B1 gene and is the second major form of congenital adrenal hyperplasia associated with hypertension. ObjectiveThe objective of this study was to screen the CYP11B1 gene for mutations in one Vietnamese male suffering from congenital adrenal hyperplasia. PatientThe patient (46,XY) had congenital adrenal hyperplasia. The clinical manifestations presented precocious puberty, hyper-pigmentation and high blood pressure at 4years. ResultsThe patient was a homozygous carrier of a novel mutation located in exon 7 containing a premature stop codon instead of tyrosine at 395 (p.Y395X). ConclusionWe have identified a novel mutant of the CYP11B1 gene in one Vietnamese family associated with phenotypes of congenital adrenal hyperplasia. The mutant gene p.Y395X produces a truncated form of the polypeptide and abolishes the enzyme activities, leading to a severe phenotype of congenital adrenal hyperplasia.

The First Vietnamese Patient with Fulminant Type 1 Diabetes Mellitus

A 23-year-old pregnant woman had a stillbirth at 30 weeks gestation due to abrupt diabetic ketoacidosis. The patient had a normal HbA1c, severe hyperglycemia, negative islet cell autoantibodies, and very low insulin secretion capacity. The viral markers associated with fulminant type 1 diabetes were negative. The patient's human leukocyte antigen genotypes were DRB1*04:06 and DQB1*03:01/05:02, not common subtypes for fulminant type 1 diabetes. This is the first Vietnamese patient with fulminant type 1 diabetes mellitus.

The first reported HLCS gene mutation causing holocarboxylase synthetase deficiency in a Vietnamese patient

Holocarboxylase synthetase deficiency is an inborn error of biotin metabolism leading to multiple carboxylase deficiency which is often biotin responsive. This disease is believed to be relatively common among the Asian population. A 6-year-old Vietnamese boy presented with recurrent episodes of severe metabolic acidosis precipitated by intercurrent illnesses. An extensive skin rash was present since the onset of his illness. Multiple carboxylase deficiency was considered a likely diagnosis based on the history and the characteristic skin rash. This diagnosis was later confirmed by urine organic acid and molecular genetic studies. Urine organic acid showed characteristic excretion of glycine conjugates. Serum biotinidase activity was normal. Sequencing of the holocarboxylase synthetase gene revealed the patient being homozygous for a common mutation R508W. The patient showed a dramatic response to biotin within days of its administration. This case illustrates a potential highly treatable inborn error of metabolism that can be recognized on clinical grounds and its favorable response to biotin treatment.

A vaccine prepared from a non-pathogenic H5N1 avian influenza virus strain confers protective immunity against highly pathogenic avian influenza virus infection in cynomolgus macaques

In order to prepare for the emergence of pandemic influenza viruses, we have established an influenza virus library that contains non-pathogenic influenza A virus strains with 135 combinations of 15 hemagglutinin and 9 neuraminidase subtypes. In this study, we developed a vaccine against H5N1 highly pathogenic avian influenza (HPAI) virus infection in humans using a virus strain selected from the library. We examined its immunogenic potency using cynomolgus macaques as a primate model. Virus antigen-specific antibodies were elicited by intranasal or subcutaneous administration of inactivated whole virus particle vaccines. After challenge with an H5N1 HPAI virus isolate obtained from a Vietnamese patient, the virus was detected only on next day following inoculation in the nasal and/or tracheal swabs of vaccinated macaques that were asymptomatic. On the other hand, the viruses were isolated from nasal and tracheal swabs from non-vaccinated macaques until day 5 and day 7 after inoculation of the H5N1 HPAI virus, respectively. Although six non-vaccinated macaques developed a high body temperature, and two of them lost their appetite after HPAI virus infection, they recovered by the end of the 12-day observation period and did not show the severe symptoms that have been reported in human H5N1 virus infection cases. This demonstrates that the vaccine prepared with the non-pathogenic H5N1 virus from our influenza virus library conferred protective immunity against H5N1 HPAI virus infection to macaques.

H5N1 Oseltamivir-resistance detection by real-time PCR using two high sensitivity labeled TaqMan probes

A single amino acid substitution, from histidine to tyrosine at position 274 of the neuraminidase gene has converted Oseltamivir sensitive H5N1 influenza A virus into a resistant strain. Currently, Oseltamivir is being stockpiled in many countries potentially affected by the influenza A virus subtype H5N1 epidemic. To identify this change in Oseltamivir-treated patients, a method based on real-time PCR using two labeled TaqMan probes was developed for its rapid detection. In order to validate the method, Oseltamivir specimen from treated (Oseltamivir-resistant strain from a Vietnamese patient, two Oseltamivir-treated tigers) and untreated subjects have been used for this study. The results thus obtained as well as those derived from clone selection and sequencing showed that TaqMan probes could clearly discriminate wild type H274 from the mutant 274Y variant. The sensitivity of this assay was as low as 10 copies/μl and allowed the detection of the mutation in a mixture of wild type and mutant. Overall, the assay based on real-time PCR with two labeled TaqMan probes described here should be useful for detecting Oseltamivir-resistant H274Y H5N1 influenza A virus in many species and various sources of specimens with high sensitivity and specificity. Such studies can address potential differences in the diagnostic outcomes between patients who develop detectable Oseltamivir resistance and those who retain only the wild type strain of H5N1.

A Mutation in RYK is a Genetic Factor for Nonsyndromic Cleft Lip and Palate

The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate. Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms. A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined. The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.

Assay to Detect H5N1 Oseltamivir Resistance

Assay to Detect H5N1 Oseltamivir Resistance

A case of avian influenza (H5N1) pulmonary infection with early expansion of lung bulla formations

Summary A 22 year old previously healthy male subject was admitted to hospital in Ho Chi Minh City, Vietnam, with fever and severe pneumonia. On interviewing the patient a recent close contact with poultry was revealed and a RT-PCR test for H5 and N1 influenza antigen was found positive following nose and throat swabs. Partial recovery was highlighted by the development of extensive bulla formations in the left lung. We herein report clinical and radiological features in a 22 year old male Vietnamese patient who developed severe acute pneumonia and in whose RT-PCR test for H5 and N1 influenza antigen was found positive following nose and throat swabs. Partial recovery was highlighted by the development of extensive bulla formations in the left lung.

Opportunistic Infections Indicating Factitious Cushing??s Syndrome

Abstract We report a case of herpetic esophagitis with candidiasis associated with factitious Cushing's syndrome in a Vietnamese patient receiving long-term glucosteroid treatment of cellulite in her country. Patients with severe iatrogenic Cushing's syndrome are at high risk for opportunistic infections. Physicians should be aware of the possible misuse of glucosteroids because patients usually deny, or are not informed, of the use of these drugs.

Hemochromatosis gene ( HFE) mutations in South East Asia: a potential for iron overload☆

Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by mutations in the HFE gene that mainly affects populations of European descent. Recently a novel mutation (IVS5+1 G→A) has been described in a Vietnamese patient with HH that was not detected in a European control population. We have developed a novel method to screen for this mutation based on restriction enzyme digestion of a PCR product using a modified forward primer. We have screened 314 Vietnamese people from several ethnic groups and 154 people from Thailand for this mutation and have detected two heterozygotes in the Vietnamese subjects (allele frequency 0.003). Analysis of these heterozygotes indicates that the mutation is on the same haplotype as that found in the original proband. Screening for the widely distributed HFE mutation, H63D, gave an allele frequency of 0.049 in the Vietnamese subjects and 0.032 in the subjects from Thailand. This is the first report of H63D allele frequencies in these populations. We suggest that the presence of the IVS5+1 G→A and H63D mutations should be considered when investigating iron overload in Vietnamese patients and those of mixed origin as co-inheritance of both mutations is likely to be a risk factor for iron overload.

A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy

PurposeTo identify the genetic defect in the M1S1 gene responsible for gelatinous droplike corneal dystrophy (GDLD) in a Vietnamese family. DesignExperimental study. MethodsBlood samples were collected from a patient and the unaffected members of a GDLD-affected family. Fifty normal unrelated subjects of Vietnamese origin were used as controls. Genomic DNA was extracted from blood leukocytes. DNA analysis of the M1S1 gene was performed using polymerase chain reaction and direct sequencing. ResultsSequencing of the M1S1 gene revealed a deletion of a 12–base-pair (bp) fragment from nucleotide positions 772 to 783 [772 to 783del(ATCTATTACCTG)], resulting in a loss of four amino acids at codons 258 to 261 (L258-liter261del). Yet, an insertion of nucleotide T in place of the missing sequence (772insT) was found. This combined mutation was homozygous in the GDLD-affected patient and heterozygous in his unaffected son and younger sister. Such genetic alteration was excluded in the control population. ConclusionThis is the first report of a mutational analysis performed in a Vietnamese patient with GDLD. In this family, the novel 772 to 783del(ATCTATTACCTG) + 772insT mutation on the M1S1 gene was well cosegregated with the phenotype and thus expected to cause GDLD. Although the M1S1 gene was responsible for GDLD in Vietnamese patients, the mutation found here is completely different from that previously reported in Japanese patients, where GDLD is most frequently seen.