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Revista Colombia Médica
Universidad del Valle - Facultad de Salud
ISSN: 0120-8322
EISSN: 0120-8322
Vol. 49, No. 2, 2018, pp. 182-187
Bioline Code: rc18047
Full paper language: English
Document type: Case Report
Document available free of charge

Revista Colombia Médica, Vol. 49, No. 2, 2018, pp. 182-187

 en Clinical and mutational spectrum of Colombian patients with Pelizaeus Merzbacher Disease
Velasco Parra, Harvy Mauricio; Maradei Anaya, Silvia Juliana; Acosta Guio, Johanna Carolina; Arteaga Diaz, Clara Eugenia & Prieto Rivera, Juan Carlos

Abstract

Case Presentation: Pelizaeus Merzbacher Disease (PMD) is an X-linked developmental defect of myelination that causes childhood chronic spastic encephalopathy. Its genetic etiology can be either a duplication (or other gene dosage alterations) or a punctual mutation at the PLP1 locus. Clinically, it presents with developmental delay, nystagmus and, spasticity, supported by neuroimaging in which the defect of myelination is evident. We present a series of seven Colombian patients diagnosed with this leucodystrophy, describing their genotypic and phenotypic characteristics and heterogeneity.
Clinical Findings: All patients included were male, 6 months to 16 years of age. Mean age at onset of symptoms was 8 months. Mean age at diagnosis was 5 years 5 months, being classic PMD most frequently diagnosed, as compared to the connatal phenotype. All cases had a primary diagnosis of developmental delay on 100%, and in 28.7% of cases, early onset nystagmus was described. 85.7% of patients had spasticity, 71.4% cerebellar signs, 57.0% hypotonia, and 28.5% had an abnormal movement disorder. Only three patients were able to achieve gait, though altered. In the two patients who had a diagnosis of connatal PMD maturational ages in danger zones according to the WHO Abbreviated Scale of Psychosocial Development were documented. All cases had abnormalities in neuroimages.
Molecular Analysis and Results: Molecular studies were used in the majority of the cases to confirm the diagnosis (85.7%). For two cases molecular confirmation was not considered necessary given their affected male brothers had already been tested. PLP1 gene dosage alterations (duplications) were found in 28.5% of the patients (two siblings), whereas three different single nucleotide variants were detected.
Clinical Relevance: According to these findings, as authors we propose the diagnostic algorithm in Colombian population to begin on a high clinical suspicion, followed by paraclinical extension, moving on to the molecular confirmation by using approaches to simultaneously sequence the PLP1 gene in order to detect point mutations and in/dels and performing a copy number variation analysis for the detection of gene dosage alterations.

Keywords
Pelizaeus Merzbacher disease; child development; developmental disorders; myelin sheath; Myelin proteolipidic protein; PLP1

 
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