Lesch-Nyhan Disease and Its Variants: Phenotypic and Mutation Spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency in Argentine Patients

Abstract Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.

"Atypical" Phenotypes of Neuronal Ceroid Lipofuscinosis: The Argentine Experience in the Genomic Era

ABSTRACT Neuronal Ceroid Lipofuscinosis (NCL) refers to a group of inherited lysosomal storage disorders characterized by the intracellular accumulation of ceroid-lipofuscin compounds and neurodegeneration. Fourteen genes are currently recognized with disease-causing DNA variants: PPT1/CLN1, TPP1/CLN2, CLN3, DNAJC5/CLN4, CLN5, CLN6, MFSD8/CLN7, CLN8, CTSD/CN10, GRN/CLN11, ATP13A2/CLN12, CTSF/CLN13, KCTD7/CLN14, TBCK/CLN15. In the frame of the Cordoba cohort, we studied N=51 cases. The aim of this paper is the observational and retrospective analysis of the "atypical" phenotypes. PCR-Sanger sequencing and/or massive exome sequencing were used as a screening methodology. One CLN1 subject showed an atypical prolonged (P) phenotype with null PPT1 activity and a heterozygous compound genotype: E5 c.451C>T, p.Arg151*/g.6302T>G (I3 c.363-3T>G). Other 11 CLN2 individuals (except one girl) showed TPP1 activity decreased to around 10% of the minimum value of the reference interval in leukocytes and saliva. The DNA variants E7 c.827A>T, p.Asp276Val and I7 c.887-10A>G were the most prevalent. One CLN8 individual showed an atypical congenital phenotype with a heterozygous combination of DNA variants: E2 c.1A>G, p.?/E3 c.792C>G, p.Asn264Lys. Massive sequencing was installed as a screening methodology for the precision diagnosis of atypical CLN1, CLN2, and CLN8 phenotypes. A genetic/phenotypic local registry is under construction.

Estado poblacional del cucarachero de pantano, Cistothorus apolinari (Passeriformes: Troglodytidae) en siete humedales de la Sabana de Bogotá, Colombia

Introduction: The Apolinar's Wren Cisthotorus apolinari is an endemic species of the Eastern Andes of Colombia currently classified as Critically Endangered (CR) at the national level and Endangered (EN) worldwide, mainly due to the degradation of wetlands, their primary habitat, and the parasitism of the nests. Objetive: Evaluate the state of the populations of C. apolinari in seven wetlands of the Sabana de Bogotá, searching to define what the areas evaluated mean that it hosts the largest population of the species and what other factors determine these population sizes. Methods Between July and December 2014 in seven wetlands we monitoring carried out using counting points and auditory censuses, the abundance of the Apolinar's Wren was recorded, the vegetation cover where the individuals were recorded and the abundances of Shiny Cowbird Molothrus bonariensis. Results: There were 63.6 h of observation and 88 counting points, obtain a nine records of C. apolinari , one individual in Tibanica, three in La Florida and five in Gualí, mainly associated with the reed Schoenoplectus californicus. None of the biotic and abiotic factors evaluated in the wetlands, were found to determine the presence of the Apolinar's Wren, but trends were present for some variables as the presence of S. californicus and Thypa spp. Conclusions: The population of C. apolinari has had a significant reduction of up to 94 %, added to a possible local extinction in the wetland of La Conejera. These results seek to provide relevant information to contribute to the formulation of effective conservation measures for the protection of the species and its habitat throughout its distribution in the country.

Estenosis glótica por sinequia de cuerdas vocales secundario a cuerpo extraño: A propósito de un caso / Stenosis glottal synechia of vocal cords for secondary to foreign body: About a case

El cuerpo extraño en vía aérea es una patología frecuente. Se presenta como un evento súbito en un niño previamente sano con manifestación de dificultad respiratoria severa. Puede ser un incidente anodino o provocar complicaciones graves. Dentro de las cuales encontramos la estenosis glótica y subglótica. Esta última puede ser congénita o adquirida, la adquirida se presenta con frecuencia posterior a intubación endotraqueal, trauma directo por cuerpo extraño o trauma externo. El tratamiento depende de su localización, naturaleza y lesiones asociadas. Describimos en este caso un lactante de 8 meses que ingiere de forma accidental cuerpo extraño, el cual se extrae de forma tardía (más de 48 horas) presentando posteriormente dificultad respiratoria, estridor y disfonía, se realiza estudio endoscópico laríngeo evidenciándose estenosis subglótica inicialmente sin afectación de cuerdas vocales, en vista de evolución tórpida en control imagenologico se evidencia afección severa de cuerdas vocales, poco frecuente en la edad pediátrica. Ameritando microcirugía laríngea.

Foreign bodies in the airway is a common condition. It comes as a sudden event in a previously healthy child with manifestation of severe respiratory distress. It may be a nondescript incident and cause serious complications such as glottic and subglottic stenosis. The latter can be congenital or acquired, the acquired type is a frequent late presentation of endotracheal intubation, direct trauma by foreign body or external trauma. Treatment depends on the location, nature and associated injuries. We describe an 8 months infant who accidentally swallowed a foreign body, which was extracted after 48 hours. Posteriorly he presented difficult breathing, stridor and dysphonia. Laryngeal endoscopic study demonstrated a subglottic stenosis with unaffected vocal cord. In view of a torpid evolution, control endoscopic study reported severe vocal cord lesion which is a rare finding in children. Laryngeal microsurgery was required for his resolution.