[Frailty as a predictor of 3-year mortality in older adult patients in long-term care in Mexico]. / Fragilidad como predictor de mortalidad a 3 años en los pacientes adultos mayores en cuidados de largo plazo en México.

INTRODUCTION: The objective of our study was to evaluate the long-term association between mortality and frailty in institutionalized patients in Mexico. Worldwide, there are limited lines of research in this population of geriatric patients and this entity generates a significant impact on the quality of life and prognosis of our patients. MATERIAL AND METHODS: It is a prospective cohort study of 81 patients in long-term care who met the selection criteria. Frailty was determined using the FRAIL scale. Data on mortality were collected during the follow-up period, and diagnosis was monitored. The risk of presenting this event was determined by logistic regression, Kaplan-Meier, and Cox proportional hazards analysis, adjusted for age and sex. RESULTS: The mean follow-up time of the patients was 36 months (1094 days), during which 33 subjects died (40.7%). In our population, at the beginning of the study the vast majority of frail patients had pathologies that independently generate risk of adverse events, disability (Barthel=30.9; SD 28.8), sarcopenia (n=40; 71.4%), one to 3 falls in the last year (n=17; 63%), ≥4 falls (n=4; 57.1%). Frail participants had a higher adjusted risk of mortality (HR 2.93; 95% CI 1.33-6.43; p=0.007). CONCLUSIONS: The frailty entity is associated in the long term with mortality in institutionalized patients in Mexico. Timely treatment and approach may allow a good prognosis and quality of life.

Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature.

Mutations in the FKRP gene result in phenotypes with severe forms of congenital muscular dystrophies (CMD) and limb-girdle muscular dystrophies. We present a Mexican patient with a pathogenic homozygous mutation in the FKRP gene (c.1387A > G, p.Asn463Asp) and CMD with radiological brain anomalies as disseminated hyperintensity lesions and discrete generalized cortical atrophy. These findings have not been reported to the best of our knowledge in other patients with the same mutation. The mutation c.1387A > G, p.Asn463Asp in the FKRP gene has been described to have a founder effect in central Mexico, since all the patients described to date are of Hispanic origin. Therefore, we emphasize studying mutations in the FKRP gene in Hispanic pediatric patients with clinical suspicion of CMD. Clinical and molecular diagnosis of specific CMD subtypes is needed to help clarify the prognosis, management, and genetic counseling to the patient and families.

An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican family.

BACKGROUND: Niemann-Pick disease type C (NP-C) is a fatal lysosomal neurodegenerative and neurovisceral disease. It is caused by defects in intracellular lipid trafficking, which lead to the accumulation of lipids and glycosphingolipids within the endosomes and lysosomes of affected individuals. Pathogenic variants of the NPC1 or NPC2 genes yield highly variable phenotypes with a time course that ranges from fetal onset (i.e., hydrops fetalis) to progressive dementia in adults. NP-C is typically inherited in an autosomal-recessive manner. To our knowledge, no previous report has identified germline mosaicism as an inheritance mechanism in NP-C. CASE PRESENTATION: We report the case of a male Mexican patient with "variant" filipin staining and a juvenile form of NP-C attributed to compound heterozygosity for two previously reported pathogenic variants of NPC1: c.[1042C>T];[2780C>T] or p.[Arg348*];[Ala927Val]. The proband's mother and healthy sister were heterozygous carriers of the c.2780C > T (exon 18) and c.1042C > T (exon 8) variants, respectively. However, direct sequencing of exons 8 and 18 of NPC1 revealed no mutation in genomic DNA obtained from the father's peripheral blood. DNA profiling ruled out the possibility of non-paternity. We were unable to obtain a sperm sample to demonstrate paternal gonadal mosaicism. NPC1 haplotype analysis using 20 linked single nucleotide variants failed to yield sufficient information to document a p.(Arg348*) NPC1 pathogenic variant-associated haplotype in the family. CONCLUSIONS: We propose that this case of NP-C involves paternal germline mosaicism. To the best of our knowledge, this has not previously been reported in NP-C.