A 26-year-old woman presenting with a history of epileptic crisis, ataxia and cognitive impairment
Authors: Guimarães Matheus Procópio , Honorato Isabella Cristina Muniz , Silva Diógenes Emanuel Dantas da , Fernandes Lucca Ferdinando Queiroz , Carvalho Pedro Henrick Guimarães , Dantas Iury Hélder Santos , Oliveira Bianca Etelvina Santos de 
Published: July 2023

A 26-year-old woman was referred to a neurology outpatient clinic due to a 9-month history of generalized tonic-clonic seizures, gradually more frequent since onset. She additionally reports developing insidiously over four years ago, an asymmetrical tremor in the upper limbs (worse on the right hand), difficulty walking, speech disorders and decreased visual acuity on the right eye. She had a past medical history of major depressive disorder, but normal neuropsychomotor development in childhood, and did not drink alcohol or smoke tobacco. There is no family history of neurological conditions (she has three brothers and two healthy children). She reports consanguinity (maternal grandparents). Upon neurological examination, the patient was alert, attention was impaired and was not oriented to place or time. Speech was scanned. Her visual acuity was decreased in the right eye (20/100), right gaze-evoked nystagmus and slow saccades. Fundi in both eyes were normal and examination of the other cranial nerves was unremarkable. Based on Medical Research Council grading, the patient had a power of 5/5 in all muscle groups of the lower and upper limbs, deep tendon reflexes in upper limbs were brisk, normal in lower limbs, and plantar responses were flexor bilaterally. Sensory exam was also unremarkable in all four limbs. Appendicular ataxia was present in all members, with rest and intention tremor in upper limbs. During gait she had a noticeable widened base, and steps were unsteady and irregular. Meningismus was absent. A minimental exam was done: 21/30 (eight years of study), with impairment mainly in attention, language and planning. Routine blood tests including full blood count, fasting glucose, B12 level, renal profile, electrolytes, liver function tests, C- reactive protein, serum protein electrophoresis, thyroid function test and erythrocyte sedimentation rate were normal. Serologic tests for syphilis (venereal disease research laboratory), viral hepatitis B and C, and HIV serology were negative. Cerebrospinal fluid analysis showed 01 white blood cell/L, protein 32, glucose 68 mg/dL and absence of oligoclonal bands. Magnetic resonance imaging (MRI) sequences showed significant cerebellar atrophy. Electroencephalogram was normal. A genetic panel was done which shows a mutation on TPP1 gene, compatible with neuronal ceroid lipofuscinosis-2 (CLN-2, OMIM #204500). Neuronal ceroid lipofuscinosis (CLN) is a progressive neurodegenerative lysosomal storage disease caused by the accumulation of lipofuscin in the cerebellum and cerebral cortex, which results in neuronal death. There is an estimated incidence of < 0.5 per 100,000 live births in Europe; in Brazil its prevalence is unknown. With the identification of molecular defects, the CLNs are classified according to the underlying gene defect, regardless of the age at onset. CLN2 is caused by a deficiency of the tripeptidyl peptidase 1 (TPP1) enzyme secondary to mutations in the CLN2 gene, being the most prevalent type observed and the only treatable one. The clinical course includes refractory epilepsy to antiepileptic medications, progressive mental regression and deterioration, ataxia, myoclonus, and visual loss. On MRI, most patients have diffuse cerebellar atrophy, corroborating the clinical finding of central nervous system progressive degeneration.