Evaluating platelet function disorders in children with bleeding tendency - A single center study.

Platelet function disorders (PFDs) are a common cause of mild bleeding tendency. However, they cannot be recognized by standard screening studies. The gold standard test for PFD is platelet aggregation, performed by light transmission aggregometry (LTA). A newer and less validated method is the closure time (CT), performed by the platelet function Analyzer 100 (PFA-100). Data regarding the validity of these tests in children are limited. The aim of this study was to evaluate the usefulness of LTA and PFA-100 for the diagnosis of pediatric patients with bleeding tendency. This retrospective study included patients one month-18 year old that had LTA tests performed at the coagulation laboratory of Rabin Medical Center between the years 2006-2015. Bleeding severity was assessed using a pediatric bleeding score. Patients were excluded from analysis if they had thrombocytopenia, thrombocytosis or coagulation factors deficiencies. One hundred and thirty-seven (137) patients were included in the analysis. The median age was 7.5 years (range one month-18 years). Most patients (93%) had a bleeding score of 2 or more. Abnormal LTA was found in 40% and prolonged CT in 23% of the patients. Abnormal LTA was significantly more common in patients with a bleeding score of 2 or more compared to patients with a lower bleeding scores (P = 0.04). No significant correlation was found between the bleeding severity and the number of agonists which induced abnormal responses (p = 0.52) or the CT (p = 0.35). Furthermore, no correlation was found between abnormal LTA and prolonged CT. To conclude, we were able to diagnose 40% of children who presented with bleeding tendency with platelet aggregation defects by LTA. Abnormal LTA was significantly more prevalent in patients with a bleeding score of 2 and above. In contrast, CT was not found to be sensitive as a screening tool for PFD. Therefore, our data extend the validity of the use of LTA for the evaluation of pediatric patients with bleeding tendency.

Establishing hospital admission criteria of pediatric Henoch-Schonlein purpura.

The current study aimed to define evidence-based admission criteria of pediatric Henoch-Schonlein purpura (HSP). In addition, we aimed to better characterize epidemiological and clinical features of pediatric HSP in Israel. We performed a retrospective cohort study of all children with HSP admitted during a 15 years period to a single pediatric department. We strictly collected the clinical data of all HSP cases. Each case was categorized as either "necessary admission" or "unnecessary admission." We compared the two groups, using initially Chi square (χ(2)) and student "t" tests, and thereafter, we employed logistic stepwise regression analysis. One hundred and sixty-three children with HSP were included. A set of six clinical criteria of which the presence of minimum one predicts the need for hospitalization were identified including: orchitis, moderate or severe abdominal pain, arthritis involving more than two joints, proteinuria, clear evidence of gastrointestinal bleeding, and inability to ambulate. In conclusion, we suggest a predictive model for the admission of pediatric patients with acute HSP. The implementation of this model can significantly reduce unnecessary admissions.

TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.

BACKGROUND: The TMEM70 gene defect was recently identified as a novel cause of autosomal recessive ATP synthase deficiency. Most of the 28 patients with TMEM70 disorder reported to date display a distinctive phenotype characterised by neonatal onset of severe muscular hypotonia hypertrophic cardiomyopathy, facial dysmorphism, profound lactic acidosis, and 3-methylglutaconic aciduria. Almost all share a common Roma descent and are homozygous for a single founder splice site mutation. METHODS: Six new patients from four separate families, with clinical and biochemical diagnosis of ATP synthase deficiency, were studied. TMEM70 sequence analysis of the three exons and their flanking splice junction consensus sequences was performed in all patients. In addition their clinical phenotype and disease course was strictly studied. RESULTS: Four novel deleterious homozygous TMEM70 mutations were identified. The previously described clinical spectrum was expanded to include infantile onset cataract, early onset gastrointestinal dysfunction and congenital hypertonia with multiple contractures resembling arthrogryposis. The first characterisation of fetal presentation of the syndrome is also provided, featuring significant intrauterine growth retardation, severe oligohydramnios, fetal hypotonia, and myocardial wall thickening. CONCLUSIONS: The current report corroborates the previously described unique phenotype of TMEM70 deficiency. The study identifies TMEM70 gene defect as a pan-ethnic disorder and further redefines it as the most common cause of nuclear-origin ATP synthase deficiency.

Severe meningoencephalitis due to late reactivation of Varicella-Zoster virus in an immunocompetent child.

Recurrent reactivation of latent Varicella-Zoster virus may cause various neurological complications including encephalitis, myelitis, stroke episodes, and meningitis. It occurs mainly in elderly or immunocompromised patients and is very rare in children. We report a 14-year girl who presented with meningoencephalitis due to reactivation of Varicella-Zoster virus 10 years after she had chickenpox and 4 years after she had zoster. Characteristic skin lesions of varicella were absent. Varicella-Zoster virus DNA was detected in cerebrospinal fluid and magnetic resonance imaging (MRI) findings were consistent with small vessel cerebral vasculitis. Treatment with acyclovir and high dose methylprednisolone resulted in near-complete neurological recovery. Although rare, Varicella-Zoster virus may reactivate to cause significant central nervous system disease even in immunocompetent children. Diagnosis depends on a high degree of suspicion because the typical rash may not associate the disease. Characteristic lesions on MRI and the presence of Varicella-Zoster virus DNA in cerebrospinal fluid are key findings for the correct diagnosis.

Is omitting post urinary-tract-infection renal ultrasound safe after normal antenatal ultrasound? An observational study.

BACKGROUND: Guidelines recommend obtaining a renal ultrasonogram (RUS) for young children after a first urinary tract infection (UTI). OBJECTIVE: The aim of the current study was to assess the concordance of prenatal and post-UTI RUS findings in children with a first simple UTI. METHODS: This was a prospective study and included all children aged 5 years or younger who were hospitalised with a first simple UTI (determined as clinical response and normalisation of temperature within 48 h on initiation of antibacterial therapy with no complications). Data were collected from each child regarding the results of prenatal and post-UTI RUS. RESULTS: Overall, 250 children were included in the study and the results of late-pregnancy and post-UTI RUS were available for 84% (n = 209). Complete concordance between the two RUS was demonstrated in 96% (n = 201). The predictive value of normal antenatal to normal post-UTI RUS was 96% (95% CI: 93% to 99%). These results include four children with mild transient pelvic dilatation. In eight children in whom renal anomalies were demonstrated only in post-UTI RUS, the influence of these anomalies on the children's management was negligible. CONCLUSIONS: Prenatal-RUS have been performed in most children <5 years old hospitalised with a first simple UTI. Concordance with post-infection tests is very high. Findings which appear only in post-infectious RUS usually have negligible effects on children's management. Thus, in such children with normal antenatal RUS omitting post-UTI RUS could be considered.

Association of chronic symptomatic neutropenia with the triple A syndrome.

Chronic neutropenia syndromes include distinct hereditary disorders with varying degrees of neutropenia. Among the more common inherited disorders associated with symptomatic neutropenia are cyclic neutropenia, severe congenital neutropenia (Kostmann disease), and Schwachman-Diamond syndrome. The authors describe a 17-year-old girl with triple A syndrome who developed a progressive decrease in the granulocyte count, finally resulting in long-standing neutropenia. Its probable pathogenesis may be related to dysfunction of ALADIN (the protein known to be mutated in triple A syndrome), resulting in abnormal nucleocytoplasmic transport of essential proteins, in myeloid precursor cells. Chronic neutropenia should therefore be considered among the clinical manifestations of triple A syndrome.

Hypereosinophilic syndrome in a child presenting as eosinophilic pharyngitis.

A 3-year-old child with idiopathic hypereosinophilic syndrome (IHES) presented with sore throat and pharyngeal exudate. Recurrent throat cultures were negative and microscopic section of the exudate revealed an extensive eosinophilic infiltration. Fourteen months later, the child still has marked hypereosinophilia and pharyngeal involvement without other organ involvement. Eosinophilic pharyngitis may be a target organ in IHES. The benign clinical course and the laboratory characteristics are described.

Association of prolonged fever and hypernatremia: rare presentation of hypothalamic/third ventricle tumor in a toddler.

The authors describe a 2-year-old boy with a clinical presentation of prolonged fever of unknown origin and severe hypernatremia. This rare association was the result of a hypothalamic/third ventricle tumor. The lesion was removed and was found to be a low-grade neuronal tumor. After surgery, the child did generally well, but hypothalamic thermoregulatory and osmoregulatory functions were not restored. These presenting symptoms, their pathophysiology, and the implications for pediatric practice are discussed.