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.     

<Emphasis Type="Italic">NPHS2</Emphasis> mutations

Objective  To uncover the frequency and the spectrum of NPHS2 mutations in Egyptian children with non familial steroid-resistant nephrotic syndrome (SRNS). Methods  Sixteen patients were screened by PCR-single-strand conformation polymorphism analysis of NPHS2 gene followed by direct sequencing. Results   NPHS2 mutations were evident in four patients (25%) who were bearing four novel mutations including two frame shift mutations (R238fs and P45fs) and two missense mutations (I136L and F216Y). There were no phenotypic or histological characteristics of patients bearing NPHS2 mutations, apart from the earlier onset of the disease, compared to those who were not bearing mutations. Conclusion   NPHS2 mutations are prevalent in Egyptian children with non-familial SRNS and this may in part explain the less favorable prognosis reported in these patients.     

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.     

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.     

A novel non-sense mutation in the <Emphasis Type="Italic">SLC2A10</Emphasis> gene of an arterial tortuosity syndrome patient of Kurdish origin

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder in which patients display tortuosity of arteries in addition to hyperextensible skin, joint laxity, and other connective tissue features. This syndrome is caused by mutations in the SLC2A10 gene. In this article we describe an ATS girl of Kurdish origin who, in addition to arterial tortuosity and connective tissue features, displays stomach displacement within the thorax and bilateral hip dislocation. Clinical details of this patient have been reported previously. Sequencing of the SLC2A10 gene identified a novel homozygous non-sense c.756C>A mutation in this patient’s DNA. This mutation in the SLC2A10 gene replaces a cysteine encoding codon with a stop signal. This is believed to cause a premature truncation of GLUT10 protein in this patient. We conclude that patients of Kurdish origin who display arterial tortuosity associated with skin hyperextensibility, joint hypermobility, and characteristic facial features may carry mutations in the SLC2A10 gene.     

<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.     

<Emphasis Type="Italic">Saccharomyces boulardii</Emphasis> in childhood

Introduction  Probiotics are live microorganisms which confer a health benefit on the host. Saccharomyces boulardii, a yeast, has been found to be an effective probiotic in double-blind placebo-controlled randomized clinical studies. Materials and methods  We reviewed the established mechanisms of actions and clinical efficacy in children of S. boulardii. Conclusions  The mechanisms of action of S. boulardii depend mainly on the inhibition of some bacterial toxins, anti-inflammatory effects, and on stimulating effects on the intestinal mucosa such as trophic effects on the brush border enzymes and immunostimulatory effects. At present, in pediatric populations, there is evidence that S. boulardii is beneficial for the treatment of acute gastroenteritis and the prevention of antibiotic-associated diarrhea. More data are needed in other indications such as traveller’s diarrhea, Helicobacter pylori eradication, and inflammatory bowel disease. S. boulardii is a yeast strain that has been extensively studied in vitro and in vivo. Recent data have opened the door for new therapeutic indications. An erratum to this article can be found at     

Comparison of community-acquired methicillin-resistant <Emphasis Type="Italic">Staphylococcus</Emphasis><Emphasis Type="Italic">aureus</Emphasis> bacteremia to other staphylococcal species in a neonatal intensive care unit

Hospital acquired infections including staphylococcal species are common in neonatal intensive care units. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was recently observed in our unit. The clinical and laboratory characteristics of all neonates with Staphylococcus aureus bacteremia during an 11-year period were retrospectively reviewed. Three groups of patients were compared: 1. Patients with CA-MRSA defined as MRSA-resistant only to beta-lactams, but sensitive to all other antibiotic groups and carried SCCmec IV. 2. Patients with multi-drug-resistant (MDR)-MRSA and 3. Patients with MSSA (methicillin-sensitive S. aureus). Forty-three neonates with documented S. aureus bacteremia were included. Of these 41 were preterm babies. Eleven infants had CA-MRSA, 20 had MDR-MRSA and 12 had MSSA bacteremia, the Panton-Valentine-Leukocidine gene (pvl-gene) was not present in any of these strains. Risk factors, clinical manifestations and laboratory tests were similar in all three groups studied. Although neonates infected with CA-MRSA were more premature and had more related diseases, the mortality rate was similar in all groups (9.1% in the CA-MRSA group). Skin infections, osteomyelitis or pneumatocele were not observed more frequently in the CA-MRSA group. We did not find significant differences in risk factors or outcomes in neonates in the three groups. One possible explanation for this observation is that the CA-MRSA outbreak strain did not contain the pvl-gene, which has been suggested to be a significant virulence factor.     

<Emphasis Type="Italic">Enterobius vermicularis</Emphasis> and perianal sepsis in children

Specific aetiological factors are responsible for a significant proportion of cases of perianal sepsis in children. A rarely implicated pathogen is Enterobius vermicularis, an obligate parasite with a ubiquitous presence in children. The authors describe two unequivocal instances of threadworm involvement in perianal sepsis, suggesting a pathophysiological basis.     

Multimodality imaging of <Emphasis Type="Italic">Candida tropicalis</Emphasis> myositis

Fungal myositis is a rare entity that has been described in immunocompromised patients. We present a boy with biopsy proven fungal myositis who was examined with multiple imaging modalities. MR imaging proved to be very effective for diagnostic purposes, while US imaging was able to provide guidance for biopsy.     

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.     

Investigation of <Emphasis Type="Italic">FGF10</Emphasis> as a candidate gene in patients with anorectal malformations and exstrophy of the cloaca

The spectrum of anorectal malformations (ARM) comprises anal stenosis, ectopic anus, recto-urogenital fistula, persistent cloaca, multisystem VACTERL (VATER associations including cardiac and limb anomalies) associations, and exstrophy of the cloaca (CE). The latter also constitutes the most severe form of the bladder exstrophy epispadias complex. Since recent data revealed that fibroblast growth factor 10 (fgf-10) invalidation in mice resulted in a genetically reproducible urorectal defect, we considered FGF10 a suitable candidate gene for ARM and CE, as the protein seems to be involved in the development of this primary developmental field. A total of 20 patients (ten with ARM and VACTERL association, respectively, and ten with CE) were analysed for genomic mutations in the coding regions and exon-intron boundaries of FGF10. Aside from a common FGF10 variant no deviation from the wild-type sequence could be detected and data obtained is not supportive of FGF10 as a genetic cause of ARMs or CE in the patients investigated. Nonetheless, mutations in possibly further upstream located promoter regions and/or unknown regulatory sequences or non-coding regions cannot be excluded. Furthermore, it cannot be ruled out that other genes involved in the signalling pathway of FGF10 may contribute to the formation of these congenital malformations.     

Antibiotic resistant <Emphasis Type="Italic"> Streptococcus pneumoniae </Emphasis>and hemolytic uremic syndrome

The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in young children and most often follows an episode of gastroenteritis caused by an enterohemorrhagic strain of Escherichia coli (O157:H7). HUS induced by Streptococcus pneumoniae (SP) is rare. We report an 18-month-old patient who presented with HUS associated with SP resistant to penicillin and cephalosporins. Conclusion:Despite a protracted course including renal failure requiring 15 days of peritoneal dialysis, her kidney function completely recovered.     

Tissue damage in rat ovaries subjected to torsion and detorsion: effects of <Emphasis Type="SmallCaps">l</Emphasis>-carnitine and <Emphasis Type="Italic">N</Emphasis>-acetyl cysteine

We aimed to evaluate histopathological changes, to detect HIF-1α staining intensities and to determine MDA levels in rat ovaries, which were subjected to torsion and detorsion and treated with l-carnitine or N-acetyl cysteine (NAC). Forty-eight prepubertal female Sprague–Dawley rats were divided into five groups (n = 8): 1, control; 2, ischemia; 3, reperfusion; 4, l-carnitine; and 5, NAC groups. In groups 3, 4 and 5, an ischemic period of 3 h was followed by reperfusion for 24 h. In groups 4 and 5, ischemia was performed and either l-carnitine or NAC was infused intraperitoneally 30 min before reperfusion. Ovarian tissues were examined histopathologically; tissue MDA levels and serum IL-6 levels were determined biochemically. HIF-1α was applied to all ovaries immunohistochemically. Total tissue damage scores, tissue MDA levels and HIF-1α scores, were significantly higher in group 2 (all P < 0.001) than group 4, and group 3 than group 4 (P < 0.001, P = 0.05 and P < 0.001, respectively). They were also significantly higher in group 2 (all P < 0.001) than group 5. When group 3 is compared to group 5, total tissue damage scores and tissue MDA levels were significantly higher in the former (P < 0.01 and P < 0.001, respectively). Serum IL-6 levels were significantly higher in group 2 when compared to groups 1, 4 and 5 (all P < 0.01). The degree of tissue damage of the torsioned ovaries decreased after a reperfusion period of 24 h in the torsioned ovaries. However, ovaries of both l-carnitine and NAC groups showed better recovery than the reperfusion group. This study was accepted for poster presentation in the 21st European Congress of Pathology, held in Istanbul, Turkey, on 8–13 September 2007.     

Identification of <Emphasis Type="Italic">DKC1</Emphasis> gene mutation in an Indian patient

Dyskeratosis congenita - X-linked variety was diagnosed in a twelve year old male child with cutaneous pigmentary changes and dystrophic changes in nails of hands and feet. His elder brother had similar nail changes and had died at twelve yr of age. We demonstrated the A353V mutation in the proband after sequencing the DKC1 gene. The mother was found to be carrier for the same mutation. She did not have any clinical manifestations. This is the commonest mutation worldwide responsible for X-linked variety of this disease and has been demonstrated for the first time in an native Indian patient.     

Pyruvate dehydrogenase deficiency: identification of a novel mutation in the <Emphasis Type="Italic">PDHA1</Emphasis> gene which responds to amino acid supplementation

The pyruvate dehydrogenase complex (PDHc) is an intramitochondrial multienzyme system, which plays a key role in aerobic glucose metabolism by catalysing the oxidative decarboxylation of pyruvate to acetyl-CoA. Genetic defects in the PDHc lead to lactic acidemia and neurological abnormalities. In the majority of the cases, the defect appears to reside in the E₁α subunit, the first catalytic component of the complex. The report is on a 6-year-old Portuguese boy with mild neurological involvement and low PDHc activity with absence of E1α on immunoblotting analysis. Molecular studies showed a novel and “de novo” mutation in the PDHA1 gene, R253G. Treatment with arginine aspartate showed complete clinical and biochemical recovery. We hypothesise that arginine aspartate acts as a chemical or pharmacological chaperone, and suggest amino acid supplementation as a possible therapy in PDHA1 mutations with mild phenotypes. Conclusion: our results encourage the use of amino acid supplementation to overcome the metabolic/biochemical changes induced by PDHA1 gene specific mutations associated with mild PDHc phenotypes.     

<Emphasis Type="Italic">Staphylococcus aureus</Emphasis> meningitis secondary to occult spinal extradural abscess

We report a rare case of spinal extradural abscess presenting as Staphylococcus aureus meningitis in a previously well child. After initial improvement with intravenous antibiotics the patient clinically deteriorated in a non-specific manner. Magnetic resonance imaging (MRI) scan of the spine revealed an occult spinal extradural abscess and urgent neurosurgical laminectomy led to full recovery. No evidence of an underlying spinal abnormality or immunodeficiency was demonstrated on investigation. A high index of suspicion is required in these cases due to the frequent absence in children of classic symptoms of spinal extradural abscess. Conclusion: we advise an urgent MRI of the head and spine in such unexplained cases of Staphylococcus aureus meningitis, to allow early diagnosis and management of occult underlying pathology. Such an approach will minimise the risk of potentially catastrophic neurological sequelae.