Acquired angioedema and<Emphasis Type="Italic"> Helicobacter pylori</Emphasis> infection in a child

We describe a 10-year-old boy with acquired Helicobacter pylori infection and simultaneous angioedema which is a rare but life-threatening condition. Our patient was hospitalised with generalised angioedema and severe circulatory shock due to extreme loss of fluids and proteins into interstitial tissues (weight gain 10 kg within 2 days, extreme haemoconcentration – haemoglobin 206 g/l, haematocrit 0.570, leucocytosis 18,300 /µl, high lactate 13.8 mmol/l) and simultaneous failure of the complement system (C3 <0.16 g/l, C4 <0.13 g/l, CH50 45 U/ml, i.e. 50% of normal value, C1 inhibitor 0.21 g/l at the lower limit). All possible known causes of angioedema were excluded (infection, allergy, auto-immune disease, NSAIDs, lymphoproliferative disease) except for the simultaneous H. pylori infection which was proven serologically and histologically. Eradication therapy led to a complete remission of the H. pylori infection. An absence of angioedema and the restoration of the complement system was later observed. To the best of our knowledge, no similar case report of a child has yet been published. Conclusion: Helicobacter pylori infection should be considered in the development of angioedema in childhood.     

Clinical implications of a slight increase in the gene dosage of <Emphasis Type="Italic">MYCN</Emphasis> in neuroblastoma determined using quantitative PCR

Introduction  Recently, determining the MYCN status in neuroblastoma (NB) using the quantitative PCR (Q-PCR) and FISH instead of the Southern blotting (SB) has been recommended. In order to assess the implications of the gene dosage of MYCN in NB, the MYCN status was evaluated using Q-PCR on DNA extracted from small areas of NB specimens obtained using laser capture microdissection (LCM). Materials and methods   MYCN gene dosages (MYCN/NAGK) were determined in 63 primary NB block samples, as well as in 243 microdissected tissues from 63 samples using Q-PCR. In 23 of 63 cases, the MYCN gene status was evaluated using FISH. Results  Nine block samples with the amplification of MYCN based on SB showed a remarkable increase of the MYCN gene dosage using Q-PCR. Twelve of 54 block samples with no amplification of MYCN based on SB showed a slight increase of the MYCN gene dosage (3.56 ≧ MYCN/NAGK > 1.84), and 8 of these 12 cases were in the advanced stage. Among these 12 cases, 1 case had several LCM areas with a high copy number of MYCN and several LCM areas which showed no increase of MYCN gene. Another case showed a slight increase in the MYCN gene dosage (3.65 ≦ MYCN/NAGK ≦ 4.82) in all LCM areas. In addition, a large number of cells with the MYCN gain were found using FISH in the block sample. In 2 other cases of 12 cases, although no LCM areas showed an increased gene dosage of MYCN, a small number of cells with MYCN amplification were found using FISH were found in the block sample. Conclusion  A slight increase in the gene dosage of MYCN detected by Q-PCR may indicate that the NB tissue contains a small number of cells with the MYCN amplification or a large number of cells with the MYCN gain, which are associated with the aggressive progression of NB.     

A palpable right lower abdominal mass due to<Emphasis Type="Italic"> Yersinia</Emphasis> mesenteric lymphadenitis

Infection by Yersinia pseudotuberculosis has become of increasing pathological importance. This report describes the case of a 12-year-old female with mesenteric lymphadenitis due to Yersinia pseudotuberculosis. The patient presented with fever, abdominal pain, and a palpable right abdominal mass. Abdominal ultrasonic imaging and computerized axial tomography (CT) revealed a mass. An exploratory laparotomy was performed, followed by appendectomy and mesenteric lymph node biopsy. The diagnosis of Yersinia infection was confirmed by serology and bacterial culture of the biopsy material. This condition should be considered in patients with a right lower abdominal mass and symptoms similar to those of appendicitis.     

Inflammatory myofibroblastic tumor of the liver due to <Emphasis Type="Italic">Μycobacterium tuberculosis</Emphasis> in an immunocompetent girl

The case of a 9-year-old girl with a Mycobacterium tuberculosis inflammatory myofibroblastic tumor (IMT) of the left lobe of the liver is reported. The tumor was surgically excised and had histological features diagnostic of IMT, a positive Ziehl-Nielsen staining for acid-fast bacilli and a positive polymerase chain reaction for Mycobacterium tuberculosis. Surgical excision of the tumor followed by anti-tuberculosis treatment for 9 months resulted in full recovery. The patient had no apparent immune disorder, and there was no evidence of extrahepatic tuberculosis. These findings make this case exceptional because IMTs, due mostly to atypical mycobacteria, have been described only in immunocompromised patients.     

Primary sternal osteomyelitis due to community-associated methicillin-resistant<Emphasis Type="Italic"> Staphylococcus aureus</Emphasis>: case report and literature review

Primary sternal osteomyelitis is a rare infectious disease in paediatric patients. It has not been previously reported as caused by community-associated methicillin-resistant Staphylococcus aureus. We describe a 9-year-old boy with a painful erythematous mid-sternal mass diagnosed as primary sternal osteomyelitis. The aetiological agent was community-associated methicillin-resistant Staphylococcus aureus, carrying a type IV staphylococcal cassette chromosome for mec. Conclusion:Methicillin resistance should be taken into considered in patient with community-associated staphylococcal infections.     

A missense mutation (G604S) in the S5/pore region of <Emphasis Type="Italic">HERG</Emphasis> causes long QT syndrome in a Chinese family with a high incidence of sudden unexpected death

Long QT syndrome (LQTS) is characterized by abnormalities in cardiac repolarization that lead to prolongation of the electrocardiographic (ECG) QT interval. Mutations in the human ether-a-go-go-related gene (HERG, KCNH2) cause the chromosome 7-linked LQT2 form of congenital LQTS, which is characterized by a prolonged QT interval and a bifid T-wave with an increased susceptibility to life-threatening cardiac arrhythmias, especially in children. We describe the genotypic and phenotypic pedigree of a large Chinese family (n = 36) in which 11 members were diagnosed with LQTS on the basis of typical ECG patterns for LQT2. Symptomatic syncopal episodes appeared in seven members of this family at a young age; an additional four members had died suddenly at ages of 18, 19, 24 and 70 years, respectively. Screening for SCN5A and HERG candidate genes identified a heterozygous missense mutation 1810G→A in exon 7 of HERG that leads to the substitution of the amino acid glycine by serine (G604S); this mutation was located in the S5/pore region of the HERG protein and was associated with a malignant phenotype. Ten of the family members carrying the mutation showed a prolongation of the corrected QT interval (QTc), and seven of these had experienced multiple syncopal episodes. The retrospective examination of documented ECG records revealed that one family member who had died suddenly also had a prolonged QT interval. This study is the first to demonstrate a close correlation between clinical phenotype and genotype with a 100% penetrance based on the pedigree of a Chinese family with LQT2. Yanmin Zhang and Nan Zhou contributed equally to this investigation.     

<Emphasis Type="Italic">Chlamydophila pneumoniae</Emphasis> Myopericarditis in a Child

An 11-year-old boy with serologically confirmed Chlamydophila pneumoniae infection presented with clinical, laboratory, and echocardiographic changes consistent with myopericarditis. No reports on C. pneumoniae myopericarditis in children are found in the medical literature. The boy, previously healthy, presented with fever, rash, constitutional symptoms, elevated acute phase reactants, elevated cardiac enzymes, and high brain natriuretic peptide levels. Hemodynamic instabilities, including hypotension and mild hypoxia, were noted. Two-dimensional echocardiographic findings showed mildly depressed left ventricular systolic function and small pericardial effusion. Requiring inotropic support, the boy was treated with azithromycin 10 mg/kg once daily for 7 days and a single dose of intravenous immunoglobulin 2 g/kg. He recovered fully with improved left ventricular systolic function before hospital discharge. An early definitive diagnosis is essential to knowing the etiology of pediatric myocarditis. Specific therapy may play role in the management and prognosis of this disorder.     

Germline mutation in the <Emphasis Type="Italic">STK11</Emphasis> gene in a girl with an ovarian Sertoli cell tumour

Introduction An ovarian Sertoli cell tumour was detected in a 4-year-old girl with gonadotrophin-independent precocious puberty. Such gonadal tumours can be associated with Peutz-Jeghers syndrome, caused by mutations in the STK11 gene. We have therefore sequenced the STK11 gene. Results Mutation analysis revealed a nonsense mutation in exon 1 (c.130A>T;p.Lys44X) of the SKT11 gene, which resulted in a truncated, inactive protein. The mutation was heterozygous in patient’s lymphocytes and almost homozygous in the tumour, indicating loss of heterozygosity. Conclusion This is the first report of a STK11 germline mutation in a girl with an ovarian Sertoli cell tumour. It remains to be shown whether this particular mutation predisposes the patient to the development of ovarian tumours.     

Early <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> infection presenting as multiple pulmonary masses: an unusual presentation in a child

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. Because most children are not imaged prior to onset of clinical symptoms, the appearance of early Mycoplasma infection has not been extensively studied. We present the case of an 11-year-old boy with large pulmonary masses incidentally detected during spine MRI evaluation for scoliosis. Eight days later, the patient developed acute respiratory symptoms, and the masses seen previously had evolved into a diffuse bronchiolitis. Diagnostic testing identified Mycoplasma pneumoniae as the likely etiology. We briefly review chest CT findings of infection by Mycoplasma and compare them to this unusual presentation of Mycoplasma pneumonia with subclinical imaging findings.     

Absence of <Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> and Signs of Atherosclerotic Cardiovascular Disease in Adolescents with Systemic Lupus Erythematosus

Patients with systemic lupus erythematosus (SLE) have accelerated atherogenesis. A recent study suggested that Chlamydia pneumoniae infection might also be a contributing factor in the development of atherogenesis in patients with SLE. The objective of this study was to investigate the possible association of C. pneumoniae infection with markers of atherosclerosis in adolescents with SLE compared with age-matched healthy controls. History and exam focused on cardiovascular risk factors were obtained from 20 patients with SLE and 20 age- and sex-matched controls. Laboratory studies included serum lipid profile and high-sensitivity C-reactive protein (hsCRP). Detection of C. pneumoniae in peripheral blood mononuclear cells (PBMCs) and in nasopharyngeal swab specimens was performed. Carotid Intima-Media Thickness (CIMT) was determined by sonography in all subjects. C. pneumoniae DNA was not detected in PBMCs of any of the patients or controls. Nasopharyngeal cultures were also negative for C. pneumoniae in all patients. CIMT was slightly higher in the SLE group (0.48 ± 0.049) compared with controls (0.454 ± 0.041, p = 0.29). There was no significant difference between the two groups in body mass index, blood pressure, hsCRP, and serum cholesterol (total, LDL and HDL). Serum triglycerides were higher in the lupus group (p = 0.03). Children and adolescents with SLE might have accelerated atherosclerosis; however, we did not observe an association with C. pneumoniae infection in this population.     

A case of <Emphasis Type="Italic">Listeria</Emphasis> meningoencephalitis complicated by hydrocephalus in an immunocompetent infant

We report a very unusual case of meningoencephalitis due to Listeria monocytogenes in a 7-month-old immunocompetent boy. Cerebrospinal fluid (CSF) culture was initially negative, but was positive on the seventh day. The disease was complicated by seizures and hydrocephalus managed with temporary ventriculostomy. The infant was discharged without obvious neurological sequelae after 30 days and developed without neurological or developmental sequelae at two years of age. Listeria is difficult to isolate and is not susceptible to third-generation cephalosporins commonly used for the empirical treatment of bacterial meningitis.     

Multiple pheochromocytomas and paragangliomas in a young patient carrying a <Emphasis Type="Italic"> SDHD </Emphasis>gene mutation

We report a 13-year-old boy with an atypical manifestation of a multilocular paraganglioma. Surgical treatment was not curative despite extirpation of a left-sided abdominal paraganglioma. After surgery, the boy experienced several hypertensive crises. Further investigations including dopamine-positron emission tomography demonstrated bilateral adrenal tumours, a further right-sided paravertebral tumour as well as bilateral cervical glomus tumours. Genetic testing revealed a germline mutation in the succinate dehydrogenase subunit D (SDHD) gene. Conclusion:The final diagnosis was familial pheochromocytoma/paraganglioma type 1 (OMIM 168000). Antihypertensive treatment was succesfull and improved the patients quality of life.     

Macrocephalic mental retardation associated with a novel C-terminal <Emphasis Type="Italic"> MECP2</Emphasis> frameshift deletion

We report a novel C-terminal MECP2 frameshift deletion (1135_1142delCCCGTG CC) in a 19-year-old woman with mental retardation and epilepsy. Preservation of language capabilities, purposeful hand use and sufficient locomotion implied an atypical variant of Rett syndrome (OMIM 312750). Occipito-frontal head circumference was large at birth (36 cm; SDS 1.7) and increased until adulthood (58.5 cm; SDS 2.3). Conclusion: Our observation indicates that head size and head growth are of limited reliability in the diagnosis of MECP2-associated phenotypes.     

Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to <Emphasis Type="Italic"> Aspergillus fumigatus </Emphasis>in patients with cystic fibrosis

An increasing incidence of allergic bronchopulmonary aspergillosis (ABPA) as a complication in patients with cystic fibrosis (CF) is reported. The objective of this retrospective case-control study was to assess potential risk factors for ABPA and for Aspergillus fumigatus sensitisation (AFS). In a group of 160 CF patients, 11 (7%) fulfilled the diagnostic criteria for ABPA and 20 (13%) had evidence of AFS. They were compared to 62 control CF patients (25 for ABPA and 37 for AFS group) without evidence of ABPA or AFS using extended matching for sex, age and weight. AFS patients had received significantly higher cumulative doses of inhaled corticosteroids than their respective controls (OR 8.0; 95% CI 1.74–63). Bronchial colonisation with Stenotrophomonas maltophilia was strongly and independently associated with ABPA (OR 20; 95% CI 2.8– infinity). A longer duration of Pseudomonas aeruginosa colonisation was independently associated with AFS (OR per year 1.50; 95% CI 1.12– infinity). Conclusion: Cystic fibrosis patients with allergic bronchopulmonary aspergillosis have a more frequent isolation of S. maltophilia in their sputum than their controls. Longer duration of colonisation with P. aeruginosa is a risk factor for Aspergillus fumigatus sensitisation. Higher cumulative doses of inhaled corticosteroids are associated with Aspergillus fumigatus sensitisation and their role as a risk factor needs to be clarified.     

Vertical transmission of <Emphasis Type="Italic">Salmonella paratyphi A</Emphasis>

Neonatal enteric fever is a rare but life-threatening illness. Patients may present with varying severity, Salmonella enterica serotype Typhi causing more severe illness than Salmonella enterica serotype Paratyphi A. Salmonella enterica serotype Paratyphi A is considered to cause milder infection with fewer complications. We report a rare case of vertical transmission of Salmonella enterica serotype Paratyphi A with severe complications and high mortality. Eventhough there are case reports of vertical transmission of Salmonella enterica serotype Typhi, to our knowledge, this is the first case report of vertical transmission of Salmonella enterica serotype ParatyphiA. The role of blood culture in accurate diagnosis and treatment is also discussed.     

Late onset subgaleal hemorrhage infection with <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis>?

We report a case of an infected subgaleal hematoma caused by an unusual micro-organism in a previously healthy 11-month-old girl. Our patient presented at the emergency department with an increasing scalp swelling for 2 weeks, and culture of the evacuated fluid yielded Streptococcus pneumoniae. Although she was born after vacuum delivery and a scalp swelling was noticed from the third day of life, this swelling disappeared completely at the age of 3 months. Parents were thoroughly questioned but we could not find out a new traumatic head event. We postulate that in our patient, a subgaleal hemorrhage developed after vacuum delivery and possibly infected 11 months later, presumably from hematogenous seeding of an acute otitis media. The patient recovered well after surgical drainage and antimicrobial therapy.     

Noonan syndrome caused by germline <Emphasis Type="Italic">KRAS</Emphasis> mutation in Taiwan: report of two patients and a review of the literature

Noonan syndrome is a highly variable disorder that has significant phenotypic overlap with Costello syndrome and cardio-facio-cutaneous syndrome. KRAS mutation was the second reported gene for Noonan syndrome. This study screened for mutation of the KRAS gene in 57 unrelated ethnic Chinese children suffering from Noonan syndrome without PTPN11 gene mutation in Taiwan. This work only identified two patients with different missense mutations (c.40G>A, p.Val14Ile; c.108A>G, p.Ile36Met) in the exon 1 of KRAS gene. This study also analyzed the characteristics of 34 reported cases involving KRAS mutations in the literature. All these patients presented with variable phenotypes, including Noonan syndrome (n = 19), cardio-facio-cutaneous syndrome (n = 7), Costello syndrome (n = 6), and Noonan/cardio-facio-cutaneous syndrome (n = 1). The phenotype of KRAS mutations was generally severe, including short stature, mental retardation, heart defects, etc. In conclusion, this investigation demonstrates that KRAS mutations are the cause in a minority of cases of Chinese patients with Noonan syndrome in Taiwan.     

Colostrum from healthy Brazilian women inhibits adhesion and contains IgA antibodies reactive with Shiga toxin-producing <Emphasis Type="Italic"> Escherichia coli</Emphasis>

Although Shiga toxin-producing Escherichia coli (STEC) has been isolated in Brazil, severe manifestations of the infection, such as haemorrhagic colitis and haemolytic-uraemic syndrome, are extremely rare in our population. Enteropathogenic Escherichia coli (EPEC) is the main aetiological agent of acute infantile diarrhoea in Brazil. There are many similarities between STEC and EPEC, such as the ability to produce attaching and effacing (A/E) lesions and some virulence-associated factors. Our aim was to investigate the presence of anti-STEC antibodies in healthy people living in an EPEC endemic area. Colostrum samples collected from 51 women living in low socio-economic conditions were analysed. Two STEC strains: O111:H- (Stx1) and O157:H7 (Stx2), and one EPEC strain (O111:H-) were used in the bacterial adhesion assays to HEp-2 cells, in the Stx1 and Stx2 cytotoxicity assays on Vero cells, in immunoblotting and in ELISA assays. All the samples strongly inhibited the adhesion of the three strains and contained SIgA antibodies reactive with antigens of EPEC O111:H-, STEC O111:H- and STEC O157:H7, mainly STEC and EPEC 94 kDa adhesin intimin. High titres of anti-LPS O111 antibodies were found in many samples. Nevertheless, the cytotoxic effect of both Stx1 and Stx2 on Vero cells was not neutralised by any sample. Conclusion: Our results suggest that Brazilian people may be exposed to Shiga toxin-producing Escherichia coli more frequently than previously thought or alternatively there may be a cross reactive immunity between enteropathogenic Escherichia coli and Shiga toxin-producing Escherichia coli.     

Long-term follow-up of a patient with primary hypomagnesaemia and secondary hypocalcaemia due to a novel <Emphasis Type="Italic">TRPM6</Emphasis> mutation

Hypomagnesaemia with secondary hypocalcaemia (HSH) is a rare condition usually presenting in the newborn period as refractory seizures, other symptoms of increased neuromuscular excitability and growth disturbances. A case with a novel TRPM6 mutation with an excellent long-term outcome is reported to highlight the observation that clinical suspicion is essential for an early diagnosis and treatment of HSH. The compliance of a long-term treatment with oral magnesium supplements is critical to avoid abnormalities of neurological and physical development. The finding of novel mutations supports the notion that the molecular study of the whole TRPM6 gene is required for diagnostic accuracy. Furthermore, the molecular study of the different types of hereditary hypomagnesaemia is critical to further improve our knowledge of magnesium homeostasis.     

Prolonged anemia by superinfection of parvovirus B19 in a boy with enterohemorrhagic <Emphasis Type="Italic">Escherichia coli</Emphasis> O157-associated hemolytic uremic syndrome

We report a 3-year-old boy with enterohemorrhagic Escherichia coli (EHEC) O157-associated hemolytic uremic syndrome (HUS). His anemia was associated with decreased reticulocyte count and persisted after the recovery from HUS. Superinfection of parvovirus B19 (PVB19) was proven by a transient febrile episode associated with IgM antibodies to the virus and the delayed appearance of IgG antibodies and typical rashes. We conclude that PVB19 infection could induce severe persistent anemia in EHEC-associated HUS. Reticulocytopenia is a clue to the diagnosis in such cases.