with a slight Neuronal ceroid lipofuscinosis: A case report

Neuronal ceroid lipofuscinoses (NCL) represent severe neurodegenera�ve condi�ons which is one of the lysosomal storage disorders. There are four main clinical forms of NCL among which late infan�le variety is the second most common condi�on. Here, we discuss a case concerning a boy aged 5 years and 4 months who exhibited a con�nuous decline in cogni�ve and motor func�ons star�ng from the age of 4. As the disorder advanced, he experienced gradual deteriora�on of his eyesight, unsteady walking and myoclonic seizures. An electroencephalogram performed on the child demonstrated widespread instances of sharp and slow wave discharges alongside a slowed background ac�vity. Magne�c resonance imaging revealed extensive cerebral and no�ceable cerebellar degenera�on. A skin biopsy extracted from the armpit area displayed dis�nc�ve eosinophilic inclusions within the cells and structures in the eccrine ducts which stained posi�vely for periodic acid-Schiﬀ. These ﬁndings indicated a possibility of neuronal ceroid lipofuscinoses


INTRODUCTION
Neuronal ceroid lipofuscinoses (NCLs) constitute a cluster of the most prevalent hereditary and childhood neurodegenerative conditions.The worldwide incidence is 1:100000. 1These conditions are identified by the buildup of self-fluorescent lipopigments within neurons and other body tissues. 2,3 linically, NCL is classified according to the age of onset into infantile, late infantile, juvenile and adult form. 3The distinctive symptoms that serve as diagnostic indicators for NCLs encompass diminished vision alongside cognitive and motor decline.These symptoms are frequently accompanied by ataxia, myoclonus, and epilepsy, ultimately leading to premature demise.To our knowledge, no case of NCL has been reported from Bangladesh.Hence, we report this case of a male child who had characteristic clinical features which lead to a suspicion of NCL.delay in motor milestones.Moreover, the parents observed considerable decline in speech, behavior, and cognitive functions along with disturbance in motor abilities.At the time of admission, he did not have neck control, only cooing was present and could not interact with family members.He had no history of perinatal insult.His elder brother had the same type of illness and died at 8 years of age.

CASE MANAGEMENT
On examination, patient was conscious, vitally stable but not interested to the surroundings.He had microcephaly and skin findings were normal.
Neurological examination showed: decreased tone and power in all limbs, reflexes were normal and gait could not be elicited.Cranial nerves were intact.Cerebellar function showed ataxia, intention tremor and nystagmus.Cardiac and respiratory system examination were normal.There was no abdominal organomegaly.2. NCL can be diagnosed by detecting characteristic intracytoplasmic eosinophilic inclusions and periodic acid schiff positive bodies within the eccrine ducts by skin punched biopsy from axilla.Diagnosis confirmation hinges on histopathology, enzymatic assays, and genetic testing.
In the case of rapid visual loss in children aged between 4 and 7 years, testing for CLN3 disease is advisable.
Ophthalmological assessment plays a vital role in diagnosing NCL and provides valuable diagnostic hints.
Typical clinical, ophthalmoscopic, EEG, and neuroimaging features can provide clues to this rare disease, assisting in the prevention of misdiagnosis and offering significant insights for genetic counselling.In this specific scenario, enzymatic assays and genetic testing were not possible, rather axillary skin biopsy was done for confirming the diagnosis.The storage material could be identified in easily accessible non-neural tissues (like skin, blood lymphocytes, and skeletal muscle) that prompted a significant shift from central nervous system to peripheral biopsies.This approach is safer. 6In cases of late infantile onset NCL, the prognosis is unfavorable, marked by a progressive disease trajectory and early mortality.No specific treatment approaches are available for any form of NCLs.The primary approach involves providing symptomatic and supportive care to mitigate the effects of seizures, dysphagia, and aspiration pneumonia. 7hile attempts have been made with interventions like bone marrow transplant, stem cell transplant and gene therapy, none have exhibited sustained positive outcomes.Managing seizures often proves to be challenging, necessitating the use of multiple medications, and newer antiepileptic drugs might offer assistance in managing hard-to-control seizures.In our instance, the frequency of seizures decreased with the administration of levetiracetam.
NCLs are a class of neurodegenerative conditions that worsen over time.High index of suspicions with progressive neurodegeneration with myoclonic epilepsy, visual loss and ataxia are crucial for the diagnosis of NCL.Genetic testing for NCL is the key investigation but it can also be diagnosed by histopathology in low resource countries.
Typically, the classic late-infantile NCL disease emerges around the age of three.Early in the progression, myoclonus and ataxia are commonly observed, succeeded by gradual declines in cognitive and motor functions.Retinopathy may not be prominently evident in the early stages and can be overlooked as the disease advances toward a more severe neurological impairment.Manifestations like spasticity, truncal hypotonia, loss of head control, persistent myoclonus, frequent seizures, and an extended state of reduced responsiveness characterize the disease until death occurs in early adolescence.Diagnosis is affirmed through histopathological examination, enzymatic assays, and genetic testing.There are no specific treatment options for any of NCLs.Treatment is mainly supportive and symptomatic.Infantile and late infantile onset NCL has a poor prognosis than that of juvenile and adult onset forms.Death occurs often due to aspiration pneumonia and seizure-related complications. 4

FIGURE 1
FIGURE 1 The electroencephalogram displayed widespread sharp and slow wave discharges at a frequency of 1-1.5 Hz

FIGURE 2
FIGURE 2 Magnetic resonance imaging of brain revealed cerebellar atrophy (Arrow) out of proportion to the cerebral atrophy (Axial T2 and Sagittal T1 sequence); Section demonstrated two eccrine ducts in cross section.The eccrine gland epithelium shows eosinophilic intracytoplasmic inclusions.Periodic acid Schiff (PAS) also highlighted these inclusions (Arrow)