Article Text

PDF
170
ADULT-ONSET NEURONAL CEROID LIPOFUSCINOSIS (KUFS DISEASE)
  1. Emeka Chuks Okonji
  1. Oxford

Abstract

Summary Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited lysosomal storage disorders – most commonly occurring in childhood – characterized by progressive, widespread neurodegeneration and intra-neuronal accumulation of autofluorescent lipopigments. Adult-onset NCL (also referred to as Kufs disease) is the rarest entity of this group, with an incidence of 1 in 1,000,000 worldwide.

The clinical presentation of Kufs disease involves any combination of progressive dementia, epilepsy, myoclonus, cerebellar and/or extrapyramidal signs. Behavioural changes are also common and visual loss is infrequent; however, the condition invariably leads to death within 15 years of the onset of symptoms.

The diagnostic challenges posed by patients with Kufs disease are two-fold. Firstly, their clinical presentation can mimic several other rare causes of progressive myoclonic epilepsy or dementia with motor deterioration. Secondly, unlike other forms of NCL, extra-neural accumulation of the hallmark lipopigments is unreliable for confirming a diagnosis of Kufs disease. This diagnosis is most reliably confirmed by invasive brain biopsy.

Mutations in the DNAJC5 gene, which has a key role in synaptic transmission, are a known cause of autosomal dominant Kufs disease. This gene encodes for cysteine string protein (CSP-α), which is located on pre-synaptic vesicles and enables the formation of SNARE-complexes – the key mediators of pre-synaptic vesicular fusion and exocytosis at the synaptic cleft. Causative mutations reduce synaptic levels of CSP-α, therefore impairing synaptic transmission.

This presentation will describe the clinical features and genetic analysis of a patient diagnosed with autosomal dominant Kufs disease in the UK.

Undergraduate prize.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.