Karina Milla-Neyra

Background: The global prevalence of Parkinson's disease (PD) is estimated to be 315 per 100,000 inhabitants, with variations across regions and depending on the epidemiological methods used. Door‐to‐door prevalence studies in Andean communities are notably underrepresented in the literature. Objective: The aim of this study was to estimate the PD prevalence in Jauja. Methods: A cross‐sectional community‐based door‐to‐door prevalence study was conducted from April 2018 to September 2019. We used a Spanish version of the 9‐item screening questionnaire (9‐item SQ). Trained interviewers conducted face‐to‐face screening surveys. Participants presenting “suspected parkinsonism” underwent further neurological assessment. PD cases responded to the LARGE‐PD questionnaire and “pesticide exposure questionnaire.” We calculated the crude prevalence, gender‐ and age‐specific rates, and age‐adjusted rates. Results: Out of 2527 eligible individuals, 1960 completed the screening survey. Of these, 563 were selected for neurological assessment, and 337 underwent neurological examination. PD was confirmed in 21 individuals, 16 of whom were identified using the 9‐item SQ with a crude prevalence of 816/100,000. We observed higher rates of PD in older age groups and in males compared to females (1.6 vs. 0.3%, P < 0.05). The age‐standardized prevalence was 566/100,000 (95% confidence interval [CI]: 496.6–635.2). Among PD cases, the most common environmental exposures were living near farming fields and pesticide exposure. Conclusions: The observed prevalence of PD in this town in the central highlands of Peru aligns with previous reports, with notably higher rates among individuals over the age of 80. Further prospective studies are warranted to investigate the potential influence of environmental factors on PD prevalence in this region.

Background: Juvenile‐onset Huntington's Disease (JoHD) or Huntington's disease (HD) with age of onset ≤20 years, is a rare clinical entity that often differs phenotypically from adult HD and represents only 1–15% of total HD cases.Objective: To characterize the genetic and clinical characteristics of 32 JoHD patients seen in a Peruvian Neurogenetics clinic from 2000–2018.Methods: This study is a retrospective clinical and genetic review. The clinical database in Lima, Peru was searched for HD patients seen in clinic between 2000 and 2018. Inclusion criteria were: (1) genetically confirmed disease; and (2) HD age of onset ≤20 years, according to the documented medical history.Results: Among 475 patients with genetically confirmed HD in the database, 32 patients (6.7%) had symptom onset at ≤20 years. Among JoHD patients with a known transmitting parent (30 of 32), paternal transmission accounted for 77% of cases. Anticipation was higher with paternal transmission compared to maternal transmission (27.5 ± 11.5 vs. 11.3 ± 7.1 years). Overall expanded CAG repeat length ranged from 44 to 110, with a mean length of 65.6 ± 15.4, and 14 (44%) cases had repeat length under 60. Of the 32 patients included in the study, 25 had detailed clinical symptomatology available, and many patients had unique clinical features such as prominent sleep disturbance (60% of patients), or parkinsonism (73%).Conclusions: This large case series of JoHD patients characterizes the Peruvian JoHD population, reports on unique familial relationships in JoHD, and highlights the varied symptomatic presentation of this rare disease.

Spinocerebellar ataxia subtypes 1, 3, and 6 (SCA1, MJD/SCA3, and SCA6) are among the most prevalent autosomal dominant cerebellar ataxias worldwide, but their relative frequencies in Peru are low. Frequency of large normal (LN) alleles at spinocerebellar ataxia-causative genes has been proposed to be associated with disease prevalence. To investigate the allelic distribution of the CAG repeat in ATXN1, ATXN3, and CACNA1A genes in a Peruvian mestizo population and examine their association with the relative frequency of SCA1, MJD/SCA3, and SCA6 across populations. We genotyped 213 healthy mestizo individuals from Northern Lima, Peru, for ATXN1, ATXN3, and CACNA1A using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE). We compared the frequency of LN alleles and relative disease frequency between populations. We also tested 40 samples for CAT repeat interruptions within the CAG tract of ATXN1. We found no association between disease frequency and population frequency of LN alleles at ATXN1 and ATXN3. All 40 ATXN1 samples tested for CAT interruptions were positive. Frequency of LN alleles at CACNA1A correlates with SCA6 frequency across several populations, but this effect was largely driven by data from a single population. Low frequency of SCA1 and MJD/SCA3 in Peru is not explained by frequency of LN alleles at ATXN1 and ATXN3, respectively. The observed correlation between CACNA1A LN alleles and SCA6 frequency requires further assessment.

Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population. The etiology underlying HL includes congenital and acquired causes; genetic factors are the main cause in over 50% of congenital cases. Pathogenic variants in the GJB2 gene are a major cause of congenital non-syndromic hearing loss (NSHL), while their distribution is highly heterogeneous in different populations. To the best of our knowledge, there is no data regarding the genetic etiologies of HL in Peru. In this study, we screened 133 Peruvian families with NSHL living in Lima. We sequenced both exons of the GJB2 gene for all probands. Seven probands with familial NSHL that remained negative for GJB2 variants underwent whole genome sequencing (WGS). We identified biallelic pathogenic variants in GJB2 in 43 probands; seven were heterozygous for only one allele. The c.427C>T variant was the most common pathogenic variant followed by the c.35delG variant. WGS revealed three novel variants in MYO15A in two probands, one of them was predicted to affect splicing and the others produce a premature stop codon. The Peruvian population showed a complex profile for genetic variants in the GJB2 gene, this particular profile might be a consequence of the admixture history in Peru.

With increasing life expectancies worldwide, providing longitudinal care for patients with neurodegenerative diseases in low-resource settings is a growing challenge.1 According to the 2015 Global Burden of Disease Study, Alzheimer disease, other dementias, and Parkinson disease together affect more than 50 million people globally.2 Furthermore, the WHO estimates that at least 60% of these cases occur in low and middle-income countries.1 Although currently available treatments for neurodegenerative diseases are largely supportive rather than curative, they can reduce morbidity and burden of disease.1 As more effective medications become available and the prevalence of neurodegenerative disease increases, the need for skilled care providers will also increase.

Introducción. La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo común, el segundo más frecuente después de la enfermedad de Alzheimer. La mutación A53T en el gen SNCA, fue la primera identificada en asociación con EP. La mayoría de casos de EP en familias con esta mutación provienen de regiones cercanas al lugar del descubrimiento original. Objetivos: Evaluar la presencia de la mutación A53T en el gen SNCA en una muestra peruana de casos con EP de incidencia familiar, esporádicos y controles sanos. Material y Métodos: Se analizaron, mediante la técnica de PCR-RFLP, las muestras de ADN de 34 casos con EP esporádico, 7 casos de EP familiar y 32 individuos control. Resultados: No se encontró la mutación A53T en la muestra analizada, por lo que se infiere que ella estaría confinada a pocas familias de origen caucásico (europeo) asociadas a aquéllas con los casos originalmente descritos. Conclusiones: La mutación A53T no sería un factor causal o primario de EP en los casos evaluados.