Synonyms:
Jansky-Bielschowsky, (Spielmeyer-Vogt-Sjogren) Batten, (Parry) Kuf, Santavori
Diagnosis:
A group of lysosomal storage disorders
Types:
Infantile INCL
Type 2: Late infantile LINCL a.k.a. Classic a.k.a. Jansky-Bielschowsky disease
Type 3: Juvenile JNCL a.k.a. Spielmeyer-Vogt-Sjogren disease, or Batten disease
Type 4: Adult ANCL a.k.a. Kuf’s disease, or Parry disease. No visual failure
Type 5: Finish variant
Genetics:
Autosomal recessive, some are Autosomal dominant
Mutation analysis confirms the diagnosis.
CLN1 gene chr. 1p32. Protein= PPT a.k.a. Batten disease. Stored protein= Sphingolipid activator proteins SAP
CLN2 gene chr. 11q15 mutations, protein= lysosomal enzyme tripeptidyl peptidase 1 . TPP1. Stored protein= Subunit c of Mitochondrial ATP synthase (SCMAS)
CLN3 gene chr. 16p12. Stored protein= SCMAS
CLN4 gene, unidentified location. Stored protein= SCMAS. Adult NCL
CLN5 gene chr. 13q21-32, a.k.a. Finish variant. Stored protein= SCMAS
CLN6 gene chr. 15q21-23, late infantile variant. Stored protein= SCMAS
CLN7 gene. Stored protein= SCMAS
CLN8 gene chr. 8p23 N, or a different Northern epilepsy. Stored protein= SCMAS
CLN9 gene. Stored protein= SCMAS
CLN10 gene a.k.a. CTSDgene chr. 11p15.5 Protein= CTSD. Stored protein= SAPs
Clinical features:
Variable from 2-40s years old
Seizure (partial or generalised), myoclonus
Loss of vision, macular degeneration. Except Kuf’s disease
Regression Or Dementia: Loss of motor function & language
Ataxia
Findings on Investigations:
ERG: abnormal.
EEG: photosensitive epilepsy (fast spike-and-wave discharges or posterior spikes) in some e.g. Adult NCL
Visual evoked potentials VEP: giant VEPs in some forms
MRI:
- Cerebral atrophy (cortical grey matter)
- T2-hyperintensity of the lobar white matter, and thinning of the cerebral cortex
- Cerebellar atrophy in Finish variant.
Enzyme analysis:
- PPT1, TPP1 or CTSD deficiency
Pathology:
Progressive degeneration of the brain and retina. Apoptosis of neurons and photoreceptors.
Rectal neurons have PAS positive inclusions
Skin biopsy (conjunctival, muscle, biopsy):
Light microscopy: vacuolations in lymphocytes. Occurs in CLN3
EM, especially eccrine secretory cell:
No deposits excludes neuroceroid lipofuscinosis NCL
Intracellular inclusions (most diagnostic feature):
- Curvilinear bodies CVB, especially late infantile NCL
- Fingerprint profiles FPP, juvenile and adult NCL
- Rectilinear profiles RL, especially in CLN3.
- Granular osmiophilic deposits. Occurs in some types. CLN3, CLN5, CLN6, CLN7, CLN8
Brain biopsy:
- EM: intracellular inclusions (most diagnostic feature) see above
- Granules, cytoplasmic: PAS positive, Sudan black B positive, autofluorescent, resistant to lipid solvants
- Neuronal loss & gliosis may occur