Rare case of Batten disease presenting with progressive Vision Loss in a Child With Cognitive Impairments

A 9-year-old girl was referred to the pediatric retina service to evaluate progressive vision loss. Her medical history included neonatal seizures. She was initially evaluated at an outside institution and was found to have bilateral symmetric vision loss with nyctalopia. The onset of the symptoms was unknown. At that time, her best-corrected visual acuity (BCVA) was 20/70 OU. The patient did not receive any ophthalmological care until 2 years later, when she was seen for marked vision loss and was noted to have a BCVA of light perception in both eyes.

When she presented to the pediatric retina service, she demonstrated poor mentation and was unable to recall simple things such as the name of her siblings. Her BCVA was light perception. Her pupils were round and reactive.

The anterior segment examination and intraocular pressures were within normal limits. Fundus autofluorescence disclosed attenuated, narrow vasculature and diffuse peripheral patchy hypoautofluorescence.

Color fundus photography showed optic disc pallor, attenuated retinal vasculature, prominent choroidal markings, and central retinal atrophy with diffusely mottled pigmentation.

Optical coherence tomography displayed decreased retinal thickness, more prominent in the inner layers, and hyper-reflective dots in the outer retinal layers. Family history included unilateral vision loss in her paternal grandmother in her late 20s. Both parents were healthy and denied consanguinity. The patient has 3 half sisters, all of whom were healthy.

The patient was diagnosed having Juvenile neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease, is a group of autosomal recessive lysosomal storage diseases characterized by lipofuscin accumulation in neural tissues including the brain and retina, causing progressive neurodegeneration and premature death. It can present during childhood or adulthood with progressive vision loss, optic nerve pallor, retinal degeneration, seizures, dementia-like symptoms, and psychomotor regression. Vision loss is the most common reason for seeking ophthalmological care.

Although several genes have been implicated, its pathophysiology is not entirely understood. Most of these genes encode for lysosomal proteins. It is hypothesized that tissues with high mitochondrial turnover are the most affected, such as the retina and optic nerve. There is no approved treatment for most types of NCL, but several are under investigation.

Most patients do not present with neurodegenerative symptoms early on, making NCL a challenging diagnosis. Keeping NCL in the differential diagnosis for retinal dystrophies can lead to a timely diagnosis and optimize patient outcomes, as these patients benefit from early multidisciplinary care, family education and close neuropsychiatric management. For this reason, it is key to differentiate it from Stargardt disease early on, which also presents with vision loss and macular dystrophy in children but has a more gradual progression and no neuropsychiatric symptoms.

This patient's history of progression from a BCVA of 20/70 to light perception in 2 years, the neurological abnormalities, and imaging findings led to the consideration of NCL over Stargardt disease. Progressive vision loss in young children can be seen in conditions including intracerebral tumors, optic neuropathies, and retinal dystrophies. However, children with NCL present with characteristically rapid progression to complete vision loss within 2 to 3 years of onset. While rapidly progressive decline in BCVA is not a diagnostic criterion for NCL, it can be useful in differentiating it from other entities. Progression to complete vision loss in children with early-onset Stargardt can take more than 10 years, in contrast with 2 to 3 years in NCL. NCL also presents with early-onset retinal thinning, ellipsoid zone loss, optic nerve pallor, and attenuated vasculature,which are all present in this patient and are not common in retinal dystrophies.

Early on, when NCL can be misdiagnosed as Stargardt, an electroretinogram could prove useful. In NCL, electroretinograms generally show profound loss of amplitude at presentation with an electronegative configuration, particularly under scotopic conditions, whereas Stargardt disease shows a near normal panretinal cone and rod function. Once neurodegeneration is noticeable, a diagnosis of NCL is favored, and genetic testing is necessary for confirmation.

Observation alone is not appropriate; family engagement with timely management is essential. Genetic testing is highly specific and noninvasive and has largely replaced muscle biopsy, which is nowadays only done in areas where molecular testing is not available.

Genetic testing confirmed the diagnosis of CLN3 NCL, and the patient was referred to a clinic specializing in NCL. The parents were informed about the condition and its prognosis, and genetic counseling for immediate family members was recommended.

Source: Ashley Lopez-Cañizares, MS; Piero Carletti, BS; Audina M. Berrocal, MD; JAMA Ophthalmology Published online June 2, 2022