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Atypical neuronal ceroid lipofuscinosis type 2 (CLN2) – a type of Latte disease which occurs later in childhood – presented with seizures, language difficulties and behavioral problems as early symptoms in a group of patients in South America, a study reported.

The results support CLN2 disease as a potential diagnosis in children with these symptoms, the scientists noted.

The study, “Revealing the clinical phenotype of atypical neuronal ceroid-lipofuscinosis disease type 2: information from the largest cohort in the world, ”Was published in the Journal of Paediatrics and Child Health.

CLN2 disease is caused by mutations in the TPP1 gene, leading to a deficiency of the enzyme encoded TPP1 needed to break down proteins in lysosomes, which are compartments within cells needed to remove waste.

Typically, TPP1 genetic mutations lead to classic late infantile type of Batten disease, with onset of symptoms at 2 to 4 years of age, including seizures, progressive nerve degeneration, and visual and motor impairment.

However, some children with CLN2 disease develop symptoms later in childhood and tend to have milder and generally variable characteristics compared to those diagnosed earlier. This atypical form is variable in the age of onset and progression of the disease, with a spectrum of symptoms, making diagnosis difficult.

Studies suggest TPP1 genetic mutations that result in a complete lack of TTP1 enzyme activity underlie the more severe classical late childhood form of the disease. In contrast, other mutations leave some TTP1 enzymatic activity leading to less severe CLN2 disease.

Although atypical forms of CLN2 disease are recognized, a description of the natural course of atypical CLN2 disease, particularly in Latin America, is lacking.

Researchers based at the Porto Alegre Clinical Hospital in Brazil, working with researchers from several countries in South America and the United Kingdom, reviewed the medical records of patients with atypical CLN2 in the region in order to identify disease presentation patterns, TTP1 enzyme activity, and genetic findings to help diagnose disease when suspected.

The study included 30 people from various counties in South America. The median age of onset was 6 years, ranging from 1 to 41 years. In this group, nine patients (30%) had affected siblings.

The first symptoms reported were seizures occurring in 14 patients (47%), followed by speech impairments in six (20%), behavioral abnormalities in two patients (7%), cognitive impairments were found in two patients (7%), one reported visual alterations (3%) and another visual hallucinations (3%).

Of 29 participants with a recorded age at onset of first symptoms, 12 (41%) experienced at least one additional symptom within a year. Eight of these patients (27%) had seizures as their first symptom. When two symptoms appeared simultaneously, cognitive decline (67%) and language difficulties (50%) occurred most often.

Symptoms that motivated parents to seek medical attention were seizures in 22 of 30 participants (73%), followed by movement disorders that included muscle spasms, decreased body movements and frequent falls, as well as abnormalities in the body. behavior, cognitive difficulties, language and visual disturbances. depreciation.

“It should be noted that the onset of seizures was the symptom that led the majority of families to seek medical attention, while more subtle symptoms such as behavioral or cognitive changes were not sufficient for the families in this study. see a doctor in the early stages of the disease, ”the researchers wrote.

An abnormal EEG – a brain activity test – was found in 18 participants (60%).

All participants were tested for TPP1 activity in dried blood spots (57%), white blood cells (40%), or in one case, saliva. Reduced enzyme activity of TPP1 was confirmed in 28 patients (93%), with eight patients showing no enzyme activity.

The diagnoses were confirmed by analysis of genetic mutations and additional tests for TPP1 enzyme activity. One patient was confirmed by analysis of the metabolite profile.

Two mutations were found most frequently in this population – 887-10A to G and 1048C to T. (Note that A refers to adenine, T to thymine, C to cytosine and G to guanine. , the four building blocks of DNA).

“The [887-10A to G] The mutation was first described in CLN2 disease in Portugal, and the authors suggested that the mutant protein might retain some residual activity, leading to a late and delayed progressive form of CLN2, ”the researchers wrote.

Three previously unknown mutations were also detected – 1226G to A, 1343C to A and 1552-1G to A. The “impact of these mutations on structure, activity and [symptoms] remains to be determined, ”the researchers wrote.

“Data from this cohort of Latin American patients with atypical CLN2 show that the potential differences between the atypical and classic phenotypes include later onset of the disease and that motor manifestations may not be as common as the first symptoms” , wrote the researchers.

“In light of the availability of a specific treatment that can modify the progression of the disease, these results reinforce the importance of clinical suspicion and investigation of CLN2 even in patients above the classical age disease onset which mainly presents seizures but also language or behavior abnormalities, ”they added.

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