Neuropsychiatric manifestations of Kufs disease

Kufs disease is a type of adult-onset neuronal ceroid lipofuscinosis (ACNL), caused by the deposition of lipopigments in the neuronal tissues.[1] The incidence of Kufs disease is 1 in 1,000,000 worldwide.[2] It presents with progressive neurological impairment, intellectual deterioration, seizures, abnormal limb movements, and eventually, early death.[2–4] Few patients present with psychiatric complaints during the initial phase which can range from subtle behavioral changes like anergy, to florid psychosis.[1] The cognitive decline can present with aggression, irrelevant speech, assaultive and disorganized behavior. A 37-year-old male, was brought in with complaints of behavioral disturbances, frequent unprovoked anger outbreaks, and assaultive behavior for 3 years. He had irrelevant talk and aimless wandering, and sometimes got lost on the way back home. He exhibited inappropriate behaviors like voiding at random places, undressing in public, and handling garbage for the past 6 months. He was unable to carry out his routine chores, was clumsy in day-to-day activities, and had difficulty following instructions. He was unable to remember his address and could not recognize his close friends and relatives, which progressed to loss of memory about self-identity. In later days, he deteriorated significantly, when he exhibited regressive symptoms like childlike talk, inappropriate smiling, throwing tantrums, and bedwetting. He expressed difficulty in comprehension and communication, and lacked emotional attachment to his family members. He gradually became highly dependent and required assistance for personal care. There was no history of seizure, loss of consciousness, involuntary movement of limbs, headache, visual defects, or any signs of infection. There was no history of substance abuse, head injury, or concurrent medications. A provisional diagnosis of early-onset frontotemporal dementia (FTD) was made, and the patient was admitted and evaluated in detail. Neurological examination revealed normal motor and sensory functions. Babinski test showed plantar flexion with withdrawal response. No abnormal involuntary limb movements were observed, and gait was normal. Dysarthria was present. Mental status examination showed impaired attention, concentration, memory, speech, and language functions. His comprehension was intact, but calculation, judgement, and abstraction were impaired. There were no psychotic symptoms. He scored 15 out of 30 in montreal cognitive assessment (MOCA) and 24 out of 30 in mini-mental state examination (MMSE), suggesting severe cognitive decline. The patient was not cooperative for the neuropsychological assessment. Exhaustive blood and urine investigations were conducted to identify any signs of infection, hormonal imbalance, or deficiencies, which revealed microcytic hypochromic anemia, elevated triglycerides, and elevated vitamin B12 levels. There was also reduced ceruloplasmin. The cerebro-spinal fluid (CSF) analysis and fundus examination were normal. Electroencephalogram (EEG) finding was a diffuse slowing of waves without any epileptiform discharges, suggestive of an encephalitic pattern, and the MRI brain showed global cerebral atrophy, with predominant involvement of frontal and temporal areas and cerebellar atrophy. Exome sequencing was done to identify autoimmune causes. The report came positive for a homogenous, likely pathogenic variant in the cathepsin F (CTSF) gene. A genetic diagnosis of autosomal recessive neuronal ceroid lipofuscinosis, type 13, Kufs type, was confirmed in the report. Hence, a diagnosis of ACNL–type B with severe cognitive decline was made. Symptomatic management was given with cognitive enhancers, benzodiazepines, and supplements. Low-dose antipsychotics were given for behavioral problems. The patient deteriorated over the years, and he attained an early demise. The duration between the onset of symptoms and his demise was about 5 years. ANCL is a rare and highly fatal lysosomal storage disorder, characterized by the accumulation of excess auto fluorescent lipofuscin-like storage material in the lysosomes of neuronal tissues, which affects the structural integrity and functioning of the cell. This eventually causes the loss of neurons and the proliferation of glial cells.[3–5] This progressive neuronal loss causes atrophic changes in the cortical grey matter, cerebellum, and subsequent ventricular enlargement.[3,6] Differentiating Kufs from FTD can be challenging due to similar clinical features like behavioral and personality changes, and executive dysfunction. The early age of onset, significant and rapidly progressing cognitive decline, and neuroimaging are the key identifiers of Kufs disease.[7] Neuroimaging also helps in differentiating various other neurodegenerative disorders.[8] Demonstration of lysosomal lipofuscin deposits is confirmatory.[2] With the advent of genetic studies, the demonstration of a specific gene mutation is the gold standard.[9] The most common gene identified in autosomal recessive Kufs is CLN6 and CTSF variant (CLN6 > CTSF).[10,11] Autosomal dominant Kufs can be caused by DNAJC5.[12] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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