Is there any treatment?
As yet, no specific treatment is known that can halt or reverse the symptoms of juvenile Batten (CLN3) disease. In April 2017 the FDA approved Brineura™ as a treatment for late infantile Batten (CLN2) disease. Gene therapy is under preclinical investigation for CLN1, CLN2, CLN3, CLN6 and CLN7 forms of Batten disease. For all forms, seizures can be reduced or controlled with anticonvulsant drugs, and psychiatric and motor problems can be managed with medication. Physical therapy and occupational therapy may help patients retain motor functioning as long as possible
What is the prognosis?
Over time, affected children suffer loss of their sight, mental impairment, worsening seizures, and progressive loss of motor skills. Eventually, those with Batten disease become bedridden, require 24-hour care, and die prematurely. How quickly symptoms develop and the length of the course of disease depends on symptom onset (classic forms of Batten).
Classic forms of Batten
| Batten form | Age of onset | End of life |
|---|---|---|
| Infantile | 6 months to 2 years old | Mid-childhood |
| Late Infantile | 2 to 4 years old | 8 to 10 years old |
| Juvenile | 5 to 10 years old | Late teens to early 20s |
| Adult | 25 to 43 years old | Normal lifespan |
What governs the age of onset?
Juvenile Batten disease was named after Frederick Batten, MA, MD, FRCP, when he reported on two sisters with the disease in 1903. 1, 2 As various forms of Batten were discovered, each was named according to its age of onset (Classic forms of Batten). This was very simple when there were only four known forms [infantile, late infantile, juvenile and adult]. However, several variant late forms were discovered complicating the matter. It wasn’t until the first genes associated with Batten disease were discovered that researchers learned that different mistakes in the same gene can result the same disease with various ages of onset. 4, 6 In other words, mistakes in the CLN1 gene can cause disease beginning in the infantile, late infantile, juvenile or adult periods (CLN Gene Defects).
Juvenile Batten disease, the focus of Beyond Batten Disease Foundation, is also called CLN3 disease. Children with CLN3 disease almost always develop symptoms in the juvenile period.5
CLN Gene Defects
| Classic Name | Gene | What does this gene make? | Reported forms and age of onset |
|---|---|---|---|
| Infantile BD | CLN1 or PPT1 | Soluble lysosomal enzyme (palmitoyl protein thioesterase 1) | CLN1 disease, infantileCLN1 disease, late infantileCLN1 disease, juvenileCLN1 disease, adult |
| Late infantile BD | CLN2 or TPP1 | Soluble lysosomal enzyme (tripeptidyl peptidase 1) | CLN2 disease, late infantileCLN2 disease, juvenile |
| Juvenile BD | CLN3 | Lysosomal & multi-organelle transmembrane protein (CLN3) | CLN3 disease, juvenileCLN3 disease, adult |
| Adult BD (or Parry or Kufs type A) | CLN4 or DNAJC5 | Soluble cysteine string protein alpha (CSPa) chaperone protein affecting synapses (CSPa) | CLN4 disease, adult autosomal dominant |
| Variant late infantile BD | CLN5 | Soluble lysosomal protein, but not an enzyme (CLN5) | CLN5 disease, late infantileCLN5 disease, juvenileCLN5 disease, adult |
| Variant late infantile BD | CLN6 | Transmembrane protein, Endoplasmic Reticulum (ER) (CLN6) | CLN6 disease, late infantile |
| Adult, Kufs | CLN6 disease, adult Kufs type A | ||
| Variant late infantile BD | CLN7 or MFSD8 | Major facilitator superfamily domain containing protein 8, Transmembrane protein; Endolysosomal transporter (CLN7/MFSD8) | CLN7 disease, late infantile |
| Variant late infantile BD | CLN8 | Transmembrane protein; ER, ER-Golgi intermediate complex (CLN8) | CLN8 disease, late infantileCLN8 disease, EPMR |
| Congenital BD | CLN10 or CTSD | Soluble lysosomal enzyme (Cathepsin D) | CLN10 disease, congenitalCLN10 disease, late infantileCLN10 disease, juvenileCLN10 disease, adult |
| CLN11 or GRN | Progranulin | CLN11 disease, adultHeterozygous mutations cause frontotemporal lobar dementia | |
| CLN12 or ATP13A2 | P-type ATPase | CLN12 disease, juvenileMutations also cause Kufor-Rakeb syndrome | |
| Adult onset BD (or Kufs Type B) | CLN13 or CTSF | Soluble lysosomal enzyme (Cathepsin F) | CLN13 disease, adult Kufs type B |
| CLN14 or KCTD7 | Potassium channel tetramerization domain-containing protein 7 | CLN14 disease, infantileMutation also causes progressive myoclonic epilepsy-3 |
Are treatments on the horizon?
Recent developments in gene therapy, enzyme replacement, and drug discovery are making clinical trials for treatments in various forms of Batten disease possible. Beyond Batten Disease Foundation is spearheading a global effort, laying the groundwork for the translation of emerging discoveries into potential medicines. See our research strategy.
References
- Batten FE. Cerebral degeneration with symmetrical changes in the maculae in two members of a family. Trans Opth Soc UK. 1903;23:386-390.
- Batten FE. Family cerebral degeneration with macular change (so-called juvenile form of family amarautic idiocy). Q J Med. 1914;7:444-454.
- Cotman SL, Karaa A, Staropoli JF, et al. Neuronal ceroid lipofuscinosis: impact of recent genetic advances and expansion of the clinicopathologic spectrum. Curr Neurol. Neurosci Rep. 2013 Aug;13(8):366.
- International Batten Disease Consortium. Isolation of a novel gene underlying Batten disease, CLN3. Cell 82. 1995;949-957.
- NCL Resource: A Gateway for Batten Disease [Internet]. London: University College London; Available from: http://www.ucl.ac.uk/ncl/batten.html.
- Vesa J, Hellsten E, Verkruyse LA, et al. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature. 1995 Aug 17;376(6541):584-7.