This document discusses adult-onset neuronal ceroid-lipofuscinosis (NCLs), also known as Kuf's disease. It is caused by mutations in the CLN gene and presents with psychomotor deterioration, epilepsy, ataxia, and reduced lifespan. The disease progresses slowly over many years, with patients becoming wheelchair-bound on average within 12 years and typically surviving for 26 years after onset.

1. Adult-Onset
Neuronal Ceroid-Lipofuscinosis (NCLs)
Ade Wijaya, MD – November 2022

2. Introduction
• Neuronal ceroid-lipofuscinosis (NCLs)
• Adult-Onset = Kuf disease
• First reported almost a century ago
• Etiology: gene CLN
Tyynelä J, Lehesjoki AE. Kufs or not Kufs: challenging diagnostics of a rare adult-onset neurodegenerative disease. Brain. 2019 Jan 1;142(1):2-5.

3. Clinical Presentation
• Psychomotor deterioration
• Epilepsy – progressive myoclonic epilepsy
• Ataxia
• Reduced lifespan
• Cognitive decline
• Progressive visual impairment  not in adult
onset
Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Mirzaa GM, Amemiya A. GeneReviews®[Internet].

4. Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B. Kufs disease due to mutation of CLN6: clinical, pathological and
molecular genetic features. Brain. 2019 Jan 1;142(1):59-69.

5. Diagnosis Criteria
(Clinical)
Berkovic SF, Staropoli JF, Carpenter S, Oliver KL, Kmoch S, Anderson GW, Damiano JA, Hildebrand MS, Sims KB, Cotman SL, Bahlo M. Diagnosis and misdiagnosis of adult neuronal ceroid
lipofuscinosis (Kufs disease). Neurology. 2016 Aug 9;87(6):579-84.

6. Diagnosis Criteria (Pathology)
Berkovic SF, Staropoli JF, Carpenter S, Oliver KL, Kmoch S, Anderson GW, Damiano JA, Hildebrand MS, Sims KB, Cotman SL, Bahlo M. Diagnosis and misdiagnosis of adult neuronal ceroid
lipofuscinosis (Kufs disease). Neurology. 2016 Aug 9;87(6):579-84.

7. Diagnosis Criteria
Berkovic SF, Staropoli JF, Carpenter S, Oliver KL, Kmoch S, Anderson GW, Damiano JA, Hildebrand MS, Sims KB, Cotman SL, Bahlo M. Diagnosis and misdiagnosis of adult neuronal ceroid
lipofuscinosis (Kufs disease). Neurology. 2016 Aug 9;87(6):579-84.

8. Disease Course
• Slowly progressive
• Becoming wheelchair-bound on average 12
years into the disease course (range 3–25;
median 13).
• Some remained ambulant 3–20 years after
disease onset
• Death occurred 8–31 years after onset.
(median survival time 26 years), these
patients were bed-ridden for many years.
Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B. Kufs disease due to mutation of CLN6: clinical, pathological and
molecular genetic features. Brain. 2019 Jan 1;142(1):59-69.

9. Summary
• Mutation CLN gene
• Psychomotor deterioration, epilepsy, ataxia,
and reduced lifespan
• Slowly progressive