A team of Italian researchers suggests that CLN3 disease, also known as juvenile Batten disease, should be included in the differential diagnosis of people with autophagic vacuolar myopathy (AVM), after describing the case of a man who received an accurate diagnosis only after undergoing a muscle biopsy.
The case report, “Autophagic vacuolar myopathy caused by a CLN3 mutation. A case report,” was published in Neuromuscular Disorders.
AVMs comprise a group of muscle disorders characterized by the presence of autophagy vacuoles — small vesicles containing cell materials that ought to be digested and recycled by special enzymes — inside muscle cells.
Previous studies have shown that some patients with Batten disease may display muscle abnormalities typically associated with AVMs, suggesting a possible link between the disorders.
Now, researchers described the case of a 29-year-old Italian man who had experienced visual problems since childhood and started having seizures, feeling extreme fatigue and showing signs of motor impairment as a teenager.
Around age 25, the patient started showing signs of progressive cognitive decline, as well as minor behavioral changes. When he was 27, a neurological examination revealed he had motor impairments and muscular atrophy. Brain magnetic resonance imaging (MRI) also found signs of mild cerebellar atrophy, while ophthalmological and cardiac examinations revealed signs of optic atrophy, vision loss and heart enlargement.
Based on this set of highly heterogeneous symptoms, clinicians initially suspected the patient had mitochondrial encephalomyopathy, a disorder in which mitochondria, the cellular compartments responsible for energy production, do not function properly, leading to an array of symptoms. But genetic analysis failed to confirm the diagnosis.
Muscle biopsy and histological analysis performed afterward showed that the size of the patient’s muscle fibers was extremely variable. Although no metabolic abnormalities were found, autophagy vacuoles containing high levels of acid phosphatase — an enzyme responsible for digesting cell materials — were detected inside muscle cells.
Genetic tests confirmed the patient had two copies of a mutated form of the CLN3 gene, associated with juvenile Batten disease.
“Taken together, the patient’s clinical features and muscle biopsy findings suggested, as an alternative diagnosis, AVM occurring in [neuronal ceroid lipofuscinoses],” researchers stated.
“We believe that information in autophagic muscle disorders should further alert clinicians to consider CLN3 in individuals with vacuolar myopathy, especially if they have visual and cardiac involvement,” they concluded.