Browsing by Subject "INFANTILE"

Sort by: Order: Results:

Now showing items 1-4 of 4
  • Senkoylu, Alpaslan; Riise, Rolf B.; Acaroglu, Emre; Helenius, Ilkka (2020)
    Management of scoliosis in young children needs a comprehensive approach because of its complexity. There are many debatable points; however, only serial casting, growing rods (including traditional and magnetically con trolled) and anterior vertebral body tethering will be discussed in this article. Serial casting is a time-gaining method for postponing surgical interventions in early onset scoliosis, despite the fact that it has some adverse effects which should be con sidered and discussed with the family beforehand. Use of growing rods is a growth-friendly surgical technique for the treatment of early onset spine deformity which allows chest growth and lung development. Magnetically controlled growing rods are effective in selected cases although they sometimes have a high number of unplanned revisions. Anterior vertebral body tethering seems to be a promising novel technique for the treatment of idiopathic scoliosis in immature cases. It provides substantial correction and continuous curve control while maintaining mobility between spinal segments. However, long-term results, adverse effects and their prevention should be clarified by future studies.
  • Knuutinen, Oula; Kousi, Maria; Suo-Palosaari, Maria; Moilanen, Jukka S.; Tuominen, Hannu; Vainionpää, Leena; Joensuu, Tarja; Anttonen, Anna-Kaisa; Uusimaa, Johanna; Lehesjoki, Anna-Elina; Vieira, Päivi (2018)
    Alexander disease (AxD) is a genetic leukodystrophy caused by GFAP mutations leading to astrocyte dysfunction. Neonatal AxD is a rare phenotype with onset in the first month of life. The proband, belonging to a large pedigree with dominantly inherited benign familial neonatal epilepsy (BFNE), had a phenotype distinct from the rest of the family, with hypotonia and macrocephaly in addition to drug-resistant neonatal seizures. The patient deteriorated and passed away at 6 weeks of age. The pathological and neuroimaging data were consistent with the diagnosis of AxD. Genetic analysis of the proband identified a novel de novo GFAP missense mutation and a KCNQ2 splice site mutation segregating with the BFNE phenotype in the family. The GFAP mutation was located in the coil 2B region of GFAP protein, similar to most neonatal-onset AxD cases with an early death. The clinical and neuroradiological features of the previously published neonatal AxD patients are presented. This study further supports the classification of neonatal-onset AxD as a distinct phenotype based on the age of onset.
  • Doccini, Stefano; Morani, Federica; Nesti, Claudia; Pezzini, Francesco; Calza, Giulio; Soliymani, Rabah; Signore, Giovanni; Rocchiccioli, Silvia; Kanninen, Katja M.; Huuskonen, Mikko T.; Baumann, Marc; Simonati, Alessandro; Lalowski, Maciej; Santorelli, Filippo M. (2020)
    CLN5 disease is a rare form of late-infantile neuronal ceroid lipofuscinosis (NCL) caused by mutations in theCLN5genethat encodes a protein whose primary function and physiological roles remains unresolved. Emerging lines of evidence point to mitochondrial dysfunction in the onset and progression of several forms of NCL, offering new insights into putative biomarkers and shared biological processes. In this work, we employed cellular and murine models of the disease, in an effort to clarify disease pathways associated with CLN5 depletion. A mitochondria-focused quantitative proteomics approach followed by functional validations using cell biology and immunofluorescence assays revealed an impairment of mitochondrial functions in different CLN5 KO cell models and inCln5−/−cerebral cortex, which well correlated with disease progression. A visible impairment of autophagy machinery coupled with alterations of key parameters of mitophagy activation process functionally linked CLN5 protein to the process of neuronal injury. The functional link between impaired cellular respiration and activation of mitophagy pathways in the human CLN5 disease condition was corroborated by translating organelle-specific proteome findings to CLN5patients’fibroblasts. Our study highlights the involvement of CLN5 in activation of mitophagy and mitochondrial homeostasis offering new insights into alternative strategies towards the CLN5 disease treatment.
  • Savarese, Marco; Torella, Annalaura; Musumeci, Olimpia; Angelini, Corrado; Astrea, Guja; Bello, Luca; Bruno, Claudio; Comi, Giacomo Pietro; Di Fruscio, Giuseppina; Piluso, Giulio; Di Iorio, Giuseppe; Ergoli, Manuela; Esposito, Gaia; Fanin, Marina; Farina, Olimpia; Fiorillo, Chiara; Garofalo, Arcomaria; Giugliano, Teresa; Magri, Francesca; Minetti, Carlo; Moggio, Maurizio; Passamano, Luigia; Pegoraro, Elena; Picillo, Ester; Sampaolo, Simone; Santorelli, Filippo Maria; Semplicini, Claudio; Udd, Bjarne; Toscano, Antonio; Politano, Luisa; Nigro, Vincenzo (2018)
    Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle diseasegenes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T > G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results. (C) 2018 Elsevier B.V. All rights reserved.