Paediatric‐onset neuronal ceroid lipofuscinosis: first symptoms and presentation at diagnosis

Abstract

Neuronal ceroid lipofuscinoses (NCLs) are rare, progressive disorders. Through this series of 20 patients with NCL, we illustrate differences between subtypes in their presenting symptoms and clinical, imaging, and electrophysiological results to raise awareness of symptom diversity. Data were available on presenting symptoms, genetics, magnetic resonance imaging (MRI), electroencephalography (including with low‐frequency intermittent photic stimulation), visual responses, and electron microscopy. Causal mutations were identified in 10 patients. Eleven patients had neuronal ceroid lipofuscinosis type 2 (CLN2) disease and their most common presenting symptom was seizures, although motor and language defects were also reported. Five patients with CLN2 disease showed abnormalities at initial MRI, but only three showed a photic response with low‐frequency stimulation. Seizures were not as common a presenting symptom in other NCL subtypes. Patients with NCLs present with diverse symptoms, which may not be characteristic in early disease stages. These signs and symptoms should lead to rapid diagnostic confirmatory testing for NCLs. What this paper adds Disease presentation is not uniform for neuronal ceroid lipofuscinoses. Characteristic clinical test results may not be identified in early disease stages.

MRI in CLN2 disease patients: Subtle features that support an early diagnosis

“…Although these features are suggestive of CLN2 disease, they are not specific and may be associated with other NCL variants. A study by Dozi eres-Puyravel et al on 20 patients with various NCLs identified cerebellar and cerebral atrophy at first MRI in patients with CLN1, CLN2 and CLN6 disease [6]. This study also found cerebellar atrophy at first MRI in patients with CLN7 and CLN11 disease [6].…”

“…A study by Dozi eres-Puyravel et al on 20 patients with various NCLs identified cerebellar and cerebral atrophy at first MRI in patients with CLN1, CLN2 and CLN6 disease [6]. This study also found cerebellar atrophy at first MRI in patients with CLN7 and CLN11 disease [6]. Nevertheless, when considered alongside clinical findings, the MRI features we have identified may provide an important clue in the early diagnosis of CLN2 disease.…”

Red flags for neuronal ceroid lipofuscinosis type 2 disease

“…Photo‐paroxysmal response (PPR) on electroencephalography induced by low‐frequency photic stimulation was previously considered as highly suggestive of NCL disorders . Dozières‐Puyravel et al found a lower rate of PPR than previous studies (33% vs 69–78%) . Such variability might be due to lack of a standardized procedure of photic stimulation, and it might be influenced by antiepileptic drugs.…”

“…3 Delayed language acquisition frequently preceded the onset of more obvious symptoms, but in most cases language delay is under-detected both by parents and general paediatricians. 2 Recently language delay has been considered a forerunner of the disease as it was retrospectively identified in 83% of patients. 3 Based on these data, the occurrence of a first seizure (any type) in a patient with a language delay may be considered a clinical red flag for the diagnosis of CLN2 disease.…”

“…Rarely, ataxia is the presenting clinical manifestation . Delayed language acquisition frequently preceded the onset of more obvious symptoms, but in most cases language delay is under‐detected both by parents and general paediatricians . Recently language delay has been considered a forerunner of the disease as it was retrospectively identified in 83% of patients .…”