RESUMO
BACKGROUND: Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. METHODS: Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. RESULTS: We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). CONCLUSIONS: In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.
RESUMO
BACKGROUND: Heterotopias are a neuronal migration disorder caused by extrinsic factors or by genetic mutations. When the location is periventricular, the most frequent genetic cause is the mutation in the "filamin A2 gene", which is X-linked. New genes for periventricular nodular heterotopia with an autosomal inheritance pattern have been recently discovered. PATIENTS: We describe two siblings. The girl, who was prenatally diagnosed ventriculomegaly, had delayed development. At 6 months, she had no head control and variable muscle tone, alternating low axial tone with jerking movements. She became microcephalic. Magnetic resonance imaging at 12 months of age revealed enlarged lateral ventricles, periventricular nodular heterotopia, thin corpus callosum, a T2-hyperintensity of the putamen and the thalamus, and a loss of volume of lenticular nucleus. At 18 months, she developed sporadic myoclonic seizures that were well controlled with valproic acid. Her younger brother also developed progressive microcephaly and psychomotor delay by 6 months. He exhibited axial hypotonia with a prominent dystonic-athetoid component. Magnetic resonance imaging at 15 months of age revealed asymmetric ventriculomegaly plus diffuse nodules lining the temporal horns, a thin corpus callosum, and hyperintensity signal in putamens. He had no seizures. RESULTS: Because of the association of microcephaly, developmental delay with dystonic movements, the imaging results, and the probable autosomal recessive inheritance pattern, genetic analysis was requested. This detected a homozygous nonsense mutation in ARFGEF2 gene, at the DNA level c.388C>T in exon 4. CONCLUSIONS: The presence of dyskinetic movements in individuals with acquired microcephaly could be a manifestation of periventricular nodular heterotopia due to ARFGEF2 mutation.
