Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations.

Genetic defects of surfactant metabolism are associated with a broad range of clinical manifestations, from neonatal respiratory distress syndrome to adult interstitial lung disease. Early therapies may improve symptoms but diagnosis is often delayed owing to phenotype and genotype variability. Our objective was to characterize the cellular/ultrastructural correlates of surfactant protein C (SP-C) mutations in children with idiopathic diffuse lung diseases. We sequenced SFTPC - the gene encoding SP-C - SFTPB and ABCA3, and analyzed morphology, ultrastructure and SP expression in lung tissue when available. We identified eight subjects who were heterozygous for SP-C mutations. Median age at onset and clinical course were variable. None of the mutations were located in the mature peptide-encoding region, but were either in the pro-protein BRICHOS or linker C-terminal domains. Although lung morphology was similar to other genetic surfactant metabolism disorders, electron microscopy studies showed specific anomalies, suggesting surfactant homeostasis disruption, plus trafficking defects in the four subjects with linker domain mutation and protein misfolding in the single BRICHOS mutation carrier in whom material was available. Immunolabeling studies showed increased proSP-C staining in all cases. In two cases, amyloid deposits could be identified. Immunochemistry and ultrastructural studies may be useful for diagnostic purposes and for genotype interpretation.

Immune tolerance induced using plasma exchange and rituximab in an infantile Pompe disease patient.

Infantile Pompe disease, resulting from deficiency of lysosomal acid α-glucosidase, requires enzyme replacement therapy with recombinant human acid α-glucosidase. Most patients develop antirecombinant human acid α-glucosidase antibodies, leading to reduced response to enzyme therapy in a subgroup of them. Aiming to improve treatment response, several immune tolerance induction strategies have been explored. We describe a patient with life-threatening infusion-associated reactions presenting anti-recombinant human acid α-glucosidase antibodies. He was successfully treated with an immune tolerance induction protocol, consisting of plasma exchange combined with a single dose of rituximab. Immediate reduction of antibody titer was obtained and enzyme therapy was resumed without infusion-associated reactions. Twenty-two months later, immunoglobulin G titer remained below 1:100. In conclusion, we applied a short-course immune tolerance induction strategy in a patient with severe infusion-associated reactions and anti-recombinant human acid α-glucosidase antibodies, leading to early and persisting reduction of antibody titer, in the absence of significant adverse events.

Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy.

OBJECTIVE: To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI). METHODS: IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months. RESULTS: EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up. CONCLUSIONS: MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.