Neuronal ceroid lipofuscinosis in the South American-Caribbean region: An epidemiological overview

Abstract

Neuronal ceroid lipofuscinoses (NCLs) comprise 13 hereditary neurodegenerative pathologies of very low frequency that affect individuals of all ages around the world. All NCLs share a set of symptoms that are similar to other diseases. The exhaustive collection of data from diverse sources (clinical, genetic, neurology, ophthalmology, etc.) would allow being able in the future to define this group with greater precision for a more efficient diagnostic and therapeutic approach. Despite the large amount of information worldwide, a detailed study of the characteristics of the NCLs in South America and the Caribbean region (SA&C) has not yet been done. Here, we aim to present and analyse the multidisciplinary evidence from all the SA&C with qualitative weighting and biostatistical evaluation of the casuistry. Seventy-one publications from seven countries were reviewed, and data from 261 individuals (including 44 individuals from the Cordoba cohort) were collected. Each NCL disease, as well as phenotypical and genetic data were described and discussed in the whole group. The CLN2, CLN6, and CLN3 disorders are the most frequent in the region. Eighty-seven percent of the individuals were 10 years old or less at the onset of symptoms. Seizures were the most common symptom, both at onset (51%) and throughout the disease course, followed by language (16%), motor (15%), and visual impairments (11%). Although symptoms were similar in all NCLs, some chronological differences could be observed. Sixty DNA variants were described, ranging from single nucleotide variants to large chromosomal deletions. The diagnostic odyssey was probably substantially decreased after medical education activities promoted by the pharmaceutical industry and parent organizations in some SA&C countries. There is a statistical deviation in the data probably due to the approval of the enzyme replacement therapy for CLN2 disease, which has led to a greater interest among the medical community for the early description of this pathology. As a general conclusion, it became clear in this work that the combined bibliographical/retrospective evaluation approach allowed a general overview of the multidisciplinary components and the epidemiological tendencies of NCLs in the SA&C region.

Keywords: South America-Caribbean; epidemiology; genotype; neuronal ceroid lipofuscinoses (NCL); phenotype.

Figure 1

The SA&C publications. Graphs showing (A) the publications per year and (B) per country, and (C) the number of individuals described per SA&C country. All types of publications in public databases were collected. The country mentioned in affiliations was taken, even if the author from SA&C was not leading the article. An increasing number of publications (mainly on CLN2) was observed in the last few years. Argentina and Brazil are the most represented regarding the number of publications and individuals described, probably due to the increasing number of professionals and centers specialized in these pathologies.

Figure 2

Diagnostic odyssey in the SA&C cohort. Bar graph showing the age of onset (mean ± SEM, blue bars) and time to diagnosis (mean ± SEM, orange bars) in the SA&C population analyzed. The age of onset could be recorded for 240 individuals, while the age at diagnosis could only be defined for 89 individuals. The table below the graph indicates de number of individuals included in each analyzed group.

Figure 3

Disease evolution of all NCL variants in the SA&C cohort. Graphs showing the age of onset (mean ± SEM) of some symptoms for each NCL genotype and phenotype in the SA&C cohort. Values were obtained directly from clinical records or publications or estimated from the information available in the bibliography. The set of symptoms collected was adapted from Lourenço et al. (11). The number of individuals analyzed for each NCL variant is shown next to the graph titles. Values of the X-axis are expressed in years.