The SCA are a group of neurodegenerative disorders with autosomal dominant inheritance pattern, with symptoms caused by dysfunction of the cerebellum and brainstem, as well as their associated pathways and connections. These manifestations affect balance, gait, speech, as well as ocular conditions due to macular and retinal degeneration. Spinocerebellar Ataxia type 2 (SCA2) is the second among the spinocerebellar ataxias with the highest prevalence worldwide, and it is in Holguín Cuba, where it reaches its highest prevalence rate. A descriptive observational study will be carried out, with the objective of evaluating the biochemical values ​​and nutritional status of patients with mild and moderate SCA2 in Holguin province in the year 2024. Analysis and synthesis to reveal the actuality of the problem that was investigated and to analyze the data and information related to it, historical-logical using for the analysis and determination of the antecedents and methodological theoretical foundation of leptospirosis, deduction - induction. The main variables studied were age, sex, BMI, biochemical and hematology analyses. The main results showed a decrease in BMI and an equal decrease in biochemical markers related to nutrition. The biochemical elements studied show a high relationship with the nutritional status of the patients. The high levels of glycemia and the low levels of cholesterol, triglycerides and albumin show a high correlation with the nutritional status of the patients.

Keywords: Ataxia type 2, SCA2, biochemical elements, nutrition

SCAs are a group of neurodegenerative disorders with an autosomal dominant inheritance pattern, with symptoms caused by dysfunction of the cerebellum and brainstem, as well as their associated pathways and connections. These manifestations affect balance, gait, speech, and eye conditions due to macular and retinal degeneration. Spinocerebellar ataxia type 2 (SCA2) is the second most prevalent spinocerebellar ataxia worldwide, and its highest prevalence is in Holguín, Cuba. More than 40 distinct genetic SCAs have been identified, which are classified according to genetic loci in the order of identification. SCA1 was the first SCA described, and other subtypes were subsequently identified sequentially. SCA is not necessarily restricted to the cerebellum and spinal cord. It can also affect other parts of the central nervous system, such as the pontine nuclei, spinal cord, peripheral nerves, cortex, basal ganglia, etc. SCA6 is restricted to the cerebellum, while SCA2 spares the cerebellum. The most common and well-defined types are SCA1, SCA2, SCA3, and SCA6, which account for more than 50% of cases, while other rare variants constitute the remainder. SCA is very complex to understand from both a genotypic and phenotypic perspective, and it is very difficult to describe all the variants at once.¹

Due to the clinical and genetic heterogeneity of this group of diseases, their identification through molecular analysis of genomic DNA obtained from a blood sample is necessary. However, a curative treatment for this group of diseases has not yet been developed. Current management focuses on symptomatic treatment and treatment of complications, in addition to providing appropriate genetic counseling by a multidisciplinary team. It is widely known that several aspects of human nutrition are important in neurodegenerative diseases.² Autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurodegenerative disorders characterized by clinical, genetic, and pathological heterogeneity. They are organized in chronological order according to their discovery. The genetic etiology of hereditary ataxias is complex due to the large number of causal mutations. These mutations can be transmitted intergenerationally following an autosomal dominant, autosomal recessive, X-linked, or mitochondrial inheritance pattern. Among hereditary ataxias, the autosomal dominant subtypes (also called spinocerebellar ataxias) are the most frequent. About 48 molecular forms are known. Most of them are caused by CAG triplet expansions in the coding regions of the respective genes that result in expanded polyglutamine domains in the mutated proteins (SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, and dentatorubral-pallidoluysian atrophy (DRPLA)). In addition, there are those caused by repeat expansions in the non-coding regions of specific genes (SCA8, SCA10, SCA12, SCA31, SCA36, SCA37), while those caused by conventional mutations are less frequent. In polyglutamine diseases, the clinical prognosis depends on the size of the polyglutamine expansion, and there is an inverse correlation between this and the age at onset of symptoms and signs of these entities. The age at onset of these diseases decreases in successive generations, which is related to an increase in the size of the expansion, a phenomenon called genetic anticipation. This leads to an earlier development of symptoms compared to the previous generation. Clinical symptoms appear during adulthood, between 20 and 40 years of age, with subsequent worsening and severe progression, culminating in wheelchair confinement, bedridden status, and death due to intercurrent illnesses associated with the progression of these conditions.^1–3

The initial symptom of these conditions is usually gait disturbances, and later, other additional manifestations are associated, such as speech disorders (cerebellar dysarthria), coordination and postural stability, as well as peripheral neuropathy, pyramidal and movement disorders. In some molecular subtypes, such as SCA2, eye movement disorders are very common. Currently, there is no curative treatment for SCAs; however, increasing knowledge of the pathophysiological mechanisms provides therapeutic targets that could potentially slow disease progression. These can be divided into pharmacological therapies, rehabilitation, gene therapy, and stem cell therapy. One of the most promising therapeutic options in hereditary spinocerebellar ataxias is the enhancement of endogenous neuroprotective mechanisms through the stimulation of the synthesis and/or functional activity of proteins with neuroprotective functions such as antioxidant enzymes, brain-derived neurotrophic factor (BDNF), growth factor (IGF) and erythropoietin (EPO), which are affected as a result of the neurodegenerative process.^4,5 In Cuba, the highest prevalence and incidence rates for SCA2 ataxia have been identified compared to other regions of the world. Likewise, there is also a high frequency of normal alleles of the ATNX2 gene, which represent unstable premutated variants and are considered reservoirs of mutated alleles that lead to the emergence of new cases. In addition, there are other types of ataxias such as SCA3 (2.06%), SCA7 (0.10%), and SCA1 (0.05%). SCA3 has been confirmed as the second most common autosomal ataxia in our country. In Cuba, prevalence rates of 31 cases per 100,000 inhabitants are reported, considering patients and preclinical carriers. SCA2 has been diagnosed in more than 120 families, involving more than 800 patients, approximately 10,000 descendants at risk of developing the disease. Holguín is the most affected province with prevalence rates exceeding 47 patients per 100,000 inhabitants and almost 200 asymptomatic carriers of the mutation per 100,000 inhabitants, followed by the province of Las Tunas whose prevalence is 22 patients per 100,000 inhabitants, while in the world the reported prevalence does not exceed 5 cases per 100,000 inhabitants.^6–8 In particular, a reduction in body mass index has been demonstrated in patients with SCA2, and body mass index is a predictor of clinical-neurological severity and disease progression.9^–11 In general, several aspects of human nutrition are relevant in the context of neurodegenerative diseases.⁶ However, in the field of polyglutamine disorders, studies aimed at evaluating the clinical neurological relevance of nutritional intake have been limited to Huntington's disease.7^,12

Among the methods for assessing nutritional intake is the 24-hour dietary recall (24hDR). Although sources of systematic error have been identified in the design and implementation of the 24hDR;13 This method is one of the most widely used in the world since it allows for estimates of current nutritional intake, is inexpensive and easy to apply, and does not require specialized interviewers.14^–23 An RD24h form was included in CERES+. The use of biochemical markers in the examination of the nutritional status of these patients provides information complementary to that obtained through other assessment methods. Their interpretation is useful at all stages of nutritional assessment, as it helps determine the status of certain body compartments, provides guidance on the level of intake, absorption, or loss of certain nutrients, and allows for the calculation of nitrogen balance. It is important to understand that various non-nutritional factors can influence analytical values, such as medications and sample collection problems, thus often diminishing the usefulness of this assessment method. It is also important to note that no single determination or group of biochemical determinations can be used, on their own, to diagnose a disorder or monitor the progress of nutritional status. The use of different technologies has made it possible to identify specific factors that contribute to malnutrition in patients with various diseases. Several studies have suggested that they should be interpreted in combination with other methods for estimating body composition, analyzing intake, and calculating requirements. From a biochemical perspective, two protein compartments are classically distinguished: somatic protein, contained in skeletal muscle, and visceral protein, contained in viscera, blood cells, and plasma. Both compartments represent approximately half of the body's protein and are primarily subject to metabolic changes. The other half corresponds to the skin and connective tissue, and biochemical assessment is not possible. Most neurodegenerative diseases have few studies that allow for the evaluation of biochemical markers in their populations. Some of these diseases, classified by the WHO as rare, lack sufficient support to address all their questions. Biochemical markers are essential in the detection and diagnosis of chronic diseases, some of which present atypically in this population. Likewise, identifying important nutritional elements helps improve the quality of life of these patients and propose general measures to prolong their abilities in the face of this new health condition. Given these questions and the need to raise awareness of this group, we have posed the following scientific problem: How do biochemical markers and nutritional status behave in patients with mild and moderate SCA2 in the province of Holguín?

General objective: To evaluate biochemical markers and nutritional status of patients with SCA2 using the Body Mass Index.

A study will be carried out descriptive observational study, with the aim of evaluating the biochemical values ​​and nutritional status of patients with mild and moderate SCA2 in the province of XXXXX in 2024. The sample will consist of 98 patients with mild and moderate AC2. The sample will be 52 patients who met the inclusion criteria.

Inclusion criteria:

• Voluntariness to participate in the research
• Address in the municipality of Holguín
• Adults between 19 and 70 years old

Exclusion criteria:

• Patients with any other degenerative disease
• Patient with a decompensated chronic disease
• History of psychiatric illness

Procedures and information collection

Document review: Bibliographic reviews were conducted and the PUBMED, SCIELO and BVS Infomed databases were used. In coordination with the statistics department, data were taken from clinical records and medical records of the institution.

Empirical: Observation.

Theorists and/or general thought processes: Analysis and synthesis to reveal the current status of the problem being investigated and to analyze the data and information related to it, using historical-logical methods for the analysis and determination of the background and theoretical-methodological foundation of leptospirosis, deduction-induction.

Statistics: For the analysis of the variables, statistical techniques of absolute numbers and percentages were used.

Variable selection:

Dependent variable: Body Mass Index

Independent variables: age, sex, weight, height, hemoglobin, leukogram, glycemia, creatinine, uric acid, cholesterol, triglycerides, serum iron, albumin.

Operationalization of variables:

Statistical techniques and processing

The data were collected and a database created using Excel for Windows XP. Statistical processing of the data was performed using an Intel Core i3 processor running Windows 7, and statistical tables were created using Microsoft Excel 2009, which allowed the categories to be grouped into tables for better analysis and understanding (Table 1).

In his study in India, Akhilesh K Sonakar, does not find relevant differences with respect to age or sex, but it draws our attention that the progression of the disease can effectively influence the age of onset.²⁴ In another of the reviewed investigations Jenish Bhandari, Pawan K Thada, Debopam Samanta coincided in a varied age group, with those over 41 years of age prevailing.²⁵ Zonta MB, Teive HAG, Camargo CHF, et al, in their study Comparing loss of balance and functional capacity among patients with SCA2, SCA3 and SCA10 show data regarding age and sex very similar to our study (Table 2).²⁶

In their research on nutrition in patients with SCA2, Jorge Saínz Yasnay, Almaguer Gotay Dennis, Rodríguez Estupiñán Annelié, et al.¹⁴ show a deterioration in BMI in these patients that is not strictly related to the intake of certain foods.²⁷ In research on pediatric cases Sartorelli J, Pomponi MG, Garone G, et al. also valued the deterioration of nutritional status as a fundamental element in the good development of patients.²⁸ One of the most innovative studies related to muscle mass is that of the authors Rodríguez Díaz J, Rodríguez Labrada R, Aguilera Rodríguez R, et al, entitled Reduction of muscle strength in spinocerebellar ataxia type 2 and its relationship with the size of the mutation, where it is recognized that the loss of muscle mass is a sign of worsening of the disease (Table 3).²⁹

In the study of Malco Rossi, Marcelo Merello Regarding ataxias in general, they show how other chronic pathologies coexist that can worsen the quality of life of these patients, without going into statistical details.³⁰ In the study in Chile by Saffie Awad Paula, Vial Undurraga Felipe, Chaná Cuevas Pedro entitled Clinical characteristics of 63 patients with ataxia, they recall the genetic origin of the disease, but do not establish antecedent variables outside of ataxia itself, this little studied element constitutes a challenge to compare how the appearance of other chronic diseases behaves in these patients.³¹ We found it valuable to refer to the study by Montes Brown J, Sánchez Cruz G, García AM, et al, on Heart Rate Variability in Spinocerebellar Ataxia Type 2. It shows that cardiovascular conditions are very frequent in these patients due to the autonomic damage caused by the disease.³² Another of the reviewed studies reports the relationship of this disease with the patient's growth and other elements such as insulin resistance that predisposes to the onset of Type 2 Diabetes Mellitus, such as the study by Sen NE, Gispert S, Auburger G. from 2017 (Table 4).³³ In this table we wanted to study the general biochemical markers that are related to the nutritional status of the patients, we can observe that albumin does not maintain elevated levels in any of the patients, however it behaves decreased in 5 of them, which could be related to current studies such as that of Suárez Llanos José Pablo.³⁴ Controversy 1. Role of albumin in nutritional assessment which in their research see a stable relationship between malnutrition and low levels of albumin.³⁴ We also consulted Ramiro's research, PR. Identification of common molecular pathways between retroviral activation/replication and spinocerebellar Ataxia type 2. In XI Scientific Conference of the Holguín Chapter of the Cuban Society of Human and Medical Genetics. which addressed the disorders in cholesterol synthesis in ataxic patients, reaching conclusions similar to ours.³⁵ Furthermore, Pérez Guerrero J, Roselló Zayas I, Hidalgo Pupo R, et al, in their study Endothelial function in patients with spinocerebellar ataxia type II showed that the association with high cholesterol and triglyceride levels and obesity predominated in patients with SCA2, not coinciding with our study.³⁶ Another of the studies reviewed is that of Marcillo Marcillo AJ, Segura Betancourt DY, Mina Ortiz JB, Lipids and their relationship with neurodegenerative diseases in adults. It shows that insulin resistance affects the ability of brain cells to use glucose, which contributes to cognitive decline and the development of neurodegenerative disorders by promoting increased glucose levels (Table 5).³⁷

In the study by Díaz JCR, Pérez CLV, Cruz GS, et al. Evaluation of neurological restoration in patients with Cuban SCA2 ataxia. Plasticity and neurological restoration, it is observed that the presence of leukopenia is common in these patients, coinciding with our study.³⁸ In their study Velázquez Palacio R, Rodríguez Labrada R, Velázquez Pérez L. Importance of zinc in the nervous system: Spinocerebellar Ataxia Type 2 mentions the relationship of zinc with leukocyte formation due to the influence of zinc on the immune system as an immunostimulant. This reinforces the idea that patients with SCA2 are more likely to have low and normal levels of leukocytes even in the presence of infectious processes.³⁹ One of the most comprehensive studies that looks at the hematological line in patients with SCA2 is that of Ramirez Garcia, Sergio Alberto, Sanchez Corona, et al. Ataxin-2, a new target in complex genetic diseases. This study shows how their statistical data match ours and demonstrates how the genetic condition influences the proper development of these cell lines.⁴⁰

Patients with mild and moderate SCA2 in Holguín show a deteriorated clinical and nutritional profile, characterized by low weight and protein-energy malnutrition, lipid abnormalities with anemia, and other comorbidities.

None.

This research was conducted in accordance with the Declaration of Helsinki and the approval of the institution's ethics committee.

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