E1331. Neuronal Ceroid Lipofuscinosis: A Rare Cause of Pediatric Neurodegeneration
The University of Texas at Dallas
UT Southwestern Medical Center
UT Southwestern Medical Center
Neuronal ceroid lipofuscinoses (NCLs) are a large group of inherited lysosomal storage disorders characterized by the accumulation of ceroid lipofuscin, an autofluorescent pigment, in neuronal and extraneuronal cells. Initially NCLs were referred collectively as Batten Disease, but fourteen human NCLs have been described, with age of onset ranging from congenital to late adult (1). The diseases are classified as ceroid lipofuscinosisneuronal (CLN) followed by a number, which deciphers the disparate mutations on different chromosomes. These disorders are also classified by the age of onset, though some forms of CLN may exhibit subtypes that have different onsets. Identification of these disorders is critical, as patients typically present with progressive vision loss followed by a decline in cognitive and motor skills, epileptic seizures, and eventually premature death (2). Moreover, a subset of NCL is the late-infantile onset NCL (LINCL), where CLN2 is the classical LINCL. The age of symptom onset is typically between 2 and 7 years, and epileptic seizures are often the initial symptom. CLN7 has a later age of onset and more intense seizures than classical LINCL (2,3). These clinical distinctions and the radiological findings of CLN7 versus the other NCL subtypes are critical for radiologists to know, as it may allow for earlier diagnosis and treatment for these rare disorders.
Educational Goals / Teaching Points
The CLN classification system is explained. Mechanisms that result in CLN are depicted. Common imaging findings in these disorders are demonstrated. The radiologist’s role in assigning the diagnosis is described.
Key Anatomic/Physiologic Issues and Imaging Findings/Techniques
Mutations in the CLN7/MFSD8 gene underlie the CLN7 variant form of LINCL. CLN7 encodes the lysosomal integral membrane protein CLN7, which has 12 transmembrane domains and belongs to the major facilitator superfamily (MFS) of proteins. MFS transporters use chemiosmotic gradients to move small solutes across the membrane (3). CLN7 localizes to lysosomes and late endosomes in neurons more than glia (4). Mutations in CLN7 lead to accumulation of glyco- and lipoproteins in lysosomes, which causes cell degeneration and gliosis (5). Autopsies have revealed significant neuron loss in the Purkinje and granule cell layers of the cerebellum, cortical layer V, the CA2 region of the hippocampus, and the ganglionic layer of the retina (4). Affected brain areas showed high levels of ceroid storage, but some areas showed storage without large-scale neuron loss (4). MRI of the brain shows progressive cortical and cerebellar atrophy (6). There is often periventricular gliosis. Patients with CLN7 also show more abnormal EEG features, such as occipital spikes, than patients with other forms. (2,3). Accumulation of glutamate/glutamine and myo- inositol with diminished N-acetylaspartate on magnetic resonance spectroscopy has been described with NCL (7).
The CLNs are a rare source of progressive neurodegeneration in children. The radiologist may be the first physician to suggest clues that can lead to molecular testing.