Distinct craniofacial‐skeletal‐dermatological dysplasia in a patient with W290C mutation in FGFR2

Mutations in the fibroblast growth factor receptor genes (FGFR) have been known to be associated with many craniosynostosis syndromes with overlapping phenotypes. We studied a 15‐year‐old Thai boy with an unspecified craniosynostosis syndrome characterized by multiple suture craniosynostoses, a persistent anterior fontanel, corneal scleralization, choanal stenosis, atresia of the auditory meatus, broad thumbs and great toes, severe scoliosis, acanthosis nigricans, hydrocephalus, and mental retardation. Radiography revealed bony ankyloses of vertebral bodies of T9–12, humero‐radio‐ulnar joints, intercarpal joints, distal interphalangeal joints of fifth fingers, fibulo‐tibial joints, intertarsal joints, and distal interphalangeal joints of the first toes. The patient was a heterozygous for a 870G → T change resulting in a W290C amino acid substitution in the extracellular domain of the fibroblast growth factor receptor 2 gene (FGFR2). This mutation has previously been reported in a patient with severe Pfeiffer syndrome type 2 that is distinct from the craniosynostosis in our patient. These findings emphasize locus, allelic, and phenotypic heterogeneity of craniofacial‐skeletal‐dermatological syndrome due to FGFR2 mutations. © 2002 Wiley‐Liss, Inc.     

Renal infarction as a presentation of austrian syndrome: thromboembolic phenomenon of pneumococcal endocarditis

ABSTRACT:: A 52-year-old unvaccinated and splenectomized man presented with fever, altered sensorium, bilateral flank pain and chest discomfort accompanied with paroxysmal atrial fibrillation with a rapid ventricular response. An abdominal computed tomography scan was performed, which revealed a right renal infarct and splenosis. Transthoracic echocardiography was performed, which demonstrated an echodense structure on the mitral valve with mitral regurgitation and a vegetation on the aortic valve with aortic regurgitation. Subsequently, he was found to have pneumococcal infective endocarditis, pneumococcal pneumonia and bacterial meningitis, namely Austrian syndrome. He underwent an early aortic valve and mitral valve repair but still had a poor clinical outcome. Renal infarction has a mortality of approximately 13.2%, which is strongly influenced by the underlying diseases and infectious complications. Medical and surgical treatment initiated in a timely manner is often inadequate. The authors report the first case of Austrian syndrome presenting with renal infarction as a clue to an embolic event associated with infective endocarditis in this study.     

Phenylketonuria detected by the neonatal screening program in Thailand

Neonatal screening for phenylketonuria (PKU) was introduced as a pilot project in Thailand from 1992--1995, and mass screening was started in 1996 by the Department of Medical Sciences, Ministry of Public Health. Blood samples were collected by heelprick on filter paper either at 48 hours of life or before discharge from the hospital. Elevated blood phenylalanine was identified by screening with the Guthrie method, then followed by the fluorometric method: All infants with a phenylalanine level equal to or greater than 4 mg/dl were recalled and retested using the fluorometric method and confirmed by plasma amino acid analysis and urinary pterins for tetrahydrobiopterin deficiency. A total of 1,062,676 newborns were screened from October 1992--March 2001, with 5 cases confirmed with PKU. The incidence was 1 in 212,535. All patients have been treated with low phenylalanine diet. The results of this study confirm the benefit of early detection and treatment of PKU through the screening program.     

Molecular characterization of type 3 (neuronopathic) Gaucher disease in Thai patients

Gaucher disease is an autosomal recessive lysosomal storage disorder due to deficiency of the lysosomal enzyme glucocerebrosidase. Three clinical phenotypes, type 1, nonneuronopathic; and types 2 and 3, acute and subacute neuronopathic are recognized. The incidence of Gaucher disease in the Thai population is unknown, but likely under-diagnosed. We performed molecular analysis in four patients, from three sibships, with type 3 Gaucher disease. Four mutant glucocerebrosidase (GBA) alleles were identified including two novel splice site mutations, IVS6-1G>C and IVS9-3C>G; both are predicted to result in truncated protein products, p.F255fsX256, and p.K464fsX487 and p.S463fsX480, respectively. One patient, homozygous for the L444P point mutation, had a "Norbottnian-like" phenotype, with more severe visceral involvement, kyphosis, barreled chest, and no neurological involvement other than supranuclear gaze palsy. These molecular studies of neuronopathic Gaucher disease will provide additional genotype-phenotype correlation particularly in non-Caucasian population.     

FGFR2 mutations among Thai children with Crouzon and Apert syndromes

Crouzon and Apert syndromes have been reported to be associated with mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) gene in various ethnic groups, but never in Southeast Asian subjects. Therefore, the authors conducted a study to characterize 11 Thai patients: four with Crouzon syndrome and seven with Apert syndrome. All cases are sporadic. Mean paternal and maternal ages were 38.7 and 28.6 years, respectively. Molecularly, all patients were found to have mutations in the FGFR2 gene. Three mutations (C278F, S347C, S351C) were detected in all Crouzon patients with two having S351C. The seven patients with Apert syndrome have either S252W or P253R mutation. The authors' findings that sporadic cases were associated with advanced paternal age and that they all had mutations in FGFR2 are consistent with previous reports. This is another observation supporting the causative role of FGFR2 mutations in Crouzon and Apert syndromes.     

Comprehensive assessment of a post-coronary bypass graft patient with cardiovascular magnetic resonance imaging and multi-detector computed tomography

Coronary bypass graft surgery (CABG) is a revascularization procedure which reduces myocardial ischemia and cardiovascular morbidity and mortality in selected patients;however, up to 40% of saphanous vein grafts may degenerate over 10 years. Although coronary angiography is the gold standard to detect graft patency and native vessel disease, sometimes it is difficult to locate the grafts resulting in increased exposure to radiation and contrast administration. This case highlights the utility of cardiac computerized tomography and magnetic resonance imaging to provide comprehensive noninvasive assessment in a patient post CABG.(J Geriatr Cardiol 2007;4:244-247.)     

Surveillance on chronic arsenic exposure in the Mekong River basin of Cambodia using different biomarkers

Thousands of Cambodia populations are currently at high risks of both toxic and carcinogenic effects through drinking arsenic-rich groundwater. In order to determine and assess the use of arsenic contents in different biological samples as biomarkers of chronic arsenic exposure from drinking arsenic-rich groundwater in Cambodia, individual scalp hair, fingernail and toenail were collected from three different provinces in the Mekong River basin of Cambodia. After washing and acid-digestion, digestate was analyzed for total arsenic by an inductively coupled plasma mass spectrometry. Chemical analysis of the acid-digested hair revealed that among 270 hair samples cut from Kandal, 78.1% had arsenic content in scalp hair (As_h) greater than the typical As_h (1.00 μg g⁻¹), indicating possible arsenic toxicity. Concurrently, 1.2% and 0.6% were found elevated in Kratie (n = 84) and Kampong Cham (n = 173), respectively. Similarly, the upper end of the ranges for arsenic contents in fingernail (As_fn) and toenail (As_tn) clipped from Kandal (fingernail n = 241; toenail n = 187) were higher than the normal arsenic content in nail (0.43–1.08 μg g⁻¹), however, none was observed elevated in both Kratie (fingernail n = 76, toenail n = 42) and Kampong Cham (fingernail n = 83; toenail n = 52). Significant positive intercorrelations between groundwater arsenic concentration (As_w), average daily dose (ADD) of arsenic, As_h, As_fn and As_tn suggest that As_h, As_fn and As_tn can be used as biomarkers of chronic arsenic exposure from drinking arsenic-rich groundwater, in which As_h is more favorable than As_fn and As_tn due to the ease of sample processing and analytical measurements, respectively.     

Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations

The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS, gene symbol: PTS) is involved in the second step of the de novo biosynthesis of tetrahydrobiopterin (BH4), which is a vital cofactor of nitric oxide synthases and three types of aromatic amino acid hydroxylases; the latter are important enzymes in the production of neurotransmitters. We conducted a study of PTS mutations in East Asia, including Taiwan, Mainland China, Japan, South Korea, the Philippines, Thailand and Malaysia. A total of 43 mutations were identified, comprising 22 previously reported mutations and 21 new discovered mutations. Among these, the c.155A>G, c.259C>T, c. 272A>G, c.286G>A and c.84-291A>G mutations were the most common PTS mutations in East Asia, while the c.58T>C and c.243G>A mutations were, respectively, specific to Filipinos and Japanese originating from Okinawa. Further studies demonstrated that each of the mutations listed above was in linkage disequilibrium to a specific allele of polymorphic microsatellite marker, D11S1347. These results suggest the presence of founder effects that have affected these frequent mutations in East Asia populations. In this context, D11S1347 should become one of the most reliable polymorphic markers for use in prenatal diagnosis among PTPS deficient families, especially where mutations are yet to be identified.