FcγRIIa and FcγRIIIa polymorphisms in childhood primary immune thrombocytopenia: implications for disease pathogenesis and outcome.

Primary immune thrombocytopenia (ITP) is the commonest acquired cause of bleeding in childhood. The aim of the present study was to evaluate the role of FcγRIIa and FcγRIIIa polymorphisms in the pathogenesis and therapeutic result of childhood ITP. The genotypic frequencies for two Fcγ receptor single-nucleotide polymorphisms, FcγRIIa-131 arginine (R) versus histidine (H) and FcγRIIIa-158 valine (V) versus phenylalanine (F) were examined in 53 children diagnosed with ITP. The genotype frequencies were compared with those of 45 healthy controls. The association between the above frequencies and disease natural course as well as therapeutic result following intravenous immunoglobulin (IVIG) administration was investigated. FcγRIIIa-158V was significantly overrepresented in children with ITP versus controls (P = 0.029), whereas no statistically significant difference was noted in FcγRIIa polymorphism distribution. No statistically significant difference was noted in the above genotype frequencies' distribution between children with newly diagnosed and chronic ITP, as well as with regards to the therapeutic result following IVIG administration. High-affinity FcγRIIIa variant (158 V) is possibly implicated in disease susceptibility, but neither of the two Fcγ receptor single-nucleotide polymorphisms seem to have any impact on chronicity or therapeutic effect of IVIG.

Standard-dose intravenous anti-D immunoglobulin versus intravenous immunoglobulin in the treatment of newly diagnosed childhood primary immune thrombocytopenia.

BACKGROUND: We conducted a study to evaluate the efficacy of intravenous (IV) anti-D against IV immunoglobulin (IVIG) in newly diagnosed immune thrombocytopenia (ITP) in children and to identify the clinical characteristics of the children most likely to benefit from one or the other treatment. PROCEDURE: Children (6 mo to 14 y) with newly diagnosed ITP and a platelet count <20,000/µL were treated either with a single bolus dose of 50 µg/kg IV anti-D or with 0.8 to 1 g/kg IVIG in a randomized manner. RESULTS: Twenty-five patients, mean age of 6.8 years, were treated either with IV anti-D (n=10) or with IVIG (n=15). Both drugs were equally efficient in raising the platelet count above 20,000/µL at 24 hours posttreatment. Children who presented with bleeding stage 1 or 2 (no mucosal bleeding) responded better to IVIG treatment, in terms of an increase in platelet count at 24 hours posttreatment (P=0.04). Hemoglobin drop was greater in the anti-D group (P=0.002). CONCLUSIONS: A single bolus dose of 50 µg/kg of IV anti-D is a safe and effective first-line treatment in newly diagnosed ITP in childhood and mucosal bleeding is a poor prognostic factor for treatment with IVIG.

Pearson syndrome in an infant heterozygous for C282Y allele of HFE gene.

BACKGROUND: Pearson syndrome is a rare mitochondrial disorder characterized by sideroblastic anemia, liver disease, renal tubulopathy and exocrine pancreas deficiency. OBSERVATIONS: We describe a female infant suffering from anemia since birth who gradually developed the complete picture of Pearson syndrome by 13 months. Iron overload was disproportionate to blood transfusions. The patient was heterozygous for HFE gene C282Y mutation (type I hemochromatosis). After an initial response to deferoxamine she presented with cutaneous zygomycosis and died after metabolic derangement and Pneumocystis jiroveci pneumonia. CONCLUSION: This is the second case of a Pearson syndrome individual who was also heterozygous for HFE gene mutation C282Y published. It is also the second case report of a Pearson patient suffering from severe iron overload and liver disease that responded to therapy with deferoxamine.

Increased prevalence of silent celiac disease among Greek epileptic children.

Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Many reports mention the association between epilepsy and celiac disease and the occasional presence of occipital corticosubcortical calcifications. We investigated 255 children with idiopathic epilepsy. Evaluation included use of routine, easily obtainable studies. Patients were screened for immunoglobulin A (IgA), immunoglobulin G (IgG) antigliadin antibodies and immunoglobulin A antitissue transglutaminase antibodies. Moreover, presence of IgA antiendomysial and antireticulin antibodies was screened. Patients with positive IgA antigliadin antibodies underwent a small intestinal biopsy. Controls consisted of 280 healthy children. Intestinal histopathologic changes, positive IgA antigliadin antibodies or IgG antigliadin antibodies, antireticulin antibodies, and antitissue transglutaminase IgA antibodies were found in five epileptic children but not in control subjects (P = 0.0241). Intracranial calcifications were not found in epileptic children with celiac disease. The findings indicate that prevalence of silent celiac disease is increased among children with idiopathic epilepsy; the type of epilepsy does not appear to play a role. Serum antitissue transglutaminase IgA antibodies could be a good marker for celiac disease screening. Occipital corticosubcortical calcifications are rarer in children with celiac disease and epilepsy.

Successful treatment of epilepsy and celiac disease with a gluten-free diet.

Celiac disease is a gluten-sensitive enteropathy, which recently has been described in association with epilepsy or other neurologic disturbances. This study describes a case of a 7-year-old female with intractable-to-treatment epilepsy and late-onset celiac disease, who was treated successfully with a gluten-free diet plus antiepileptic therapy. It is important for children with intractable cases of epilepsy and weight loss to undergo screening for celiac disease.

Lissencephaly and mongolian spots in Hurler syndrome.

Hurler disease or syndrome is a disorder of mucopolysaccharide metabolism, inherited as an autosomal recessive trait. We describe a case of a 15-month-old female exhibiting with clinical and laboratory characteristics of the syndrome, central nervous system lesions (lissencephaly, excessive ventricular enlargement and Dandy Walker malformation with vermis atrophy, cerebellar cyst) and mongolian spots in the trunk and extremities. The combination of mongolian spots and severe central nervous system lesions in Hurler syndrome is considered a rare clinical occurrence, while the association with lissencephaly has never been reported.

An antiregurgitation milk formula in the management of infants with mild to moderate gastroesophageal reflux.

BACKGROUND: Thickened milk formulas are used to treat infants with gastroesophageal reflux (GER), but these substances often increase the duration of reflux episodes and worsen symptoms, and they have been associated with diarrhea, constipation, and cough. OBJECTIVES: The aims of this study were to determine the efficacy of an antiregurgitation milk formula in the clinical and laboratory setting in infants with proved GER, to investigate any possible adverse events (cough and change in the number of bowel movements or the consistency of stools), and to identify its effects on height and body weight. METHODS: Infants with recurrent vomiting and GER who were not responsive to standard treatment were eligible for the study. Infants in the treatment group (group A) were managed for 4 weeks with a specific antiregurgitation milk formula (with cornstarch and an increased amount of casein), and those in the control group (group B) were given a standard milk formula. The number of episodes of vomiting, regurgitation, and cough, as well as the frequency and consistency of stool, height, and body weight were noted at least 10 days before and during the study. A second pH monitoring was performed after 4 weeks in both groups. RESULTS: Fifty-six infants (30 boys, 26 girls; mean [SD] age, 3.1 [1.2] months) were included in the study; 30.4% had mild GER; 44.6%, moderate GER; and 25.0%, severe GER. Significantly more infants in group A than in group B (50.0% vs 14.3%, respectively) with mild or moderate GER had normal findings on the second pH monitoring (P<0.05). Changes in the reflux index and in the mean number of vomiting and regurgitation episodes were significantly different between the 2 groups (P<0.05). No significant differences in changes in the mean number of bowel movements and cough events or in the consumption time of the 2 formulas were found between the 2 groups. CONCLUSION: Infants with mild or moderate GER can be managed effectively with this antiregurgitation milk formula. Improved clinical and laboratory findings were seen in the majority of infants, and the formula was well tolerated, without adverse events.