What is Batten disease?

Batten disease is a rare, fatal, inherited disorder of the nervous system that typically begins in childhood. The first symptom is usually progressive vision loss in previously healthy children followed by personality changes, behavioral problems and slow learning. Seizures commonly appear within 2-4 years of vision loss. However, seizures and psychosis can appear at any time during the course of disease. Progressive loss of motor functions (movement and speech) start with clumsiness, stumbling and Parkinson-like symptoms; eventually, those affected become wheelchair-bound, are bedridden, and die prematurely.1,2

Juvenile Batten disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). Over 400 different errors (mutations) in 13 segments of DNA (genes) have been attributed to various forms of Batten, which differ from one another primarily by when symptoms first appear (Batten Chart).8,17,18,19,26 These disorders all affect the nervous system with increasing seizures, movement disorders, altered thought processes, and cognitive decline. Childhood NCLs also include vision loss but adult onset Batten typically do not.5,7,10,13,20,25 Although Batten disease was originally used to describe only the juvenile form, the term “Batten disease” is widely used in the US and UK to refer to all forms of NCL.

Juvenile Batten disease

The first noticeable sign of juvenile Batten disease is often loss of vision, which begins between the ages of 5 and 10 years in previously healthy children and tends to worsen rapidly.6 Other early signs are more subtle and include personality changes, behavioral problems, and slowed learning.1,15 Recurrent seizures typically begin around age 9 and motor problems appear in the early to late teenage years.2 At first, children may stumble or shuffle, followed by Parkinson-like symptoms followed by a complete decline in mobility.3,24 Disrupted sleep and psychiatric conditions may appear at any time during the course of the disease.14,16 Some affected teenagers and young adults have cardiac problems that require pacemakers.12,21 Eventually, young adults become blind, bedridden, and physically and mentally incapacitated, requiring 24-hour care until premature death in their early twenties to thirties.1,4,17

For more on understanding the CLN3 gene, whose mutations are responsible for juvenile Batten disease, click here.

For more on diagnosing juvenile Batten disease click here.

How common is juvenile Batten disease?

While a worldwide incidence rate is difficult to confirm, individual studies in various countries suggest rates range from 0.5 – 8 per 100,000 live births, with an average of 1.2 per 100,000.22,23 Evidence suggests that juvenile Batten disease is the most common form of pediatric neurodegenerative disease.9 Approximately 440,000 people in the United States [do not have any symptoms but] carry disease-causing mutations in their juvenile Batten disease (CLN3) gene.9 According to the National Human Genome Research Institute, Juvenile Batten disease is one of 6,800 rare diseases affecting 30 million or almost 1 out of every 10 Americans.11

References

  1. Aberg LE, Autti T, Braulke T et al. The Neuronal Ceroid Lipofuscinoses (Batten Disease). 2nd Oxford University Press; c2011. Chapter 8, CLN3; 110-139.
  2. Aberg LE, Backman M, Kirveskari E, et al. Epilepsy and Antiepileptic Drug Therapy in Juvenile Neuronal Ceroid Lipofuscinosis. Epilepsia. 2000b; 41(10):1296-1302.
  3. Aberg LE, Liewendahl K, Nikkinen P, et al. Decreased striatal dopamine transporter density in JNCL patients with parkinsonian symptoms. Neurology. 2000a Mar 14;54(5):1069-74.
  4. Backman ML, Santavuori PR, Aberg LE, et al. Psychiatric symptoms of children and adolescents with juvenile neuronal ceroid lipofuscinosis. J Intellect Disabil Res. 2005 Jan;49(Pt1):25-32.
  5. Boehme DH, Cottrell JC, Leonberg SC, et al. A dominant form of neuronal ceroid-lipofuscinosis. Brain. 1971;94:745–760.
  6. Bozorg S, Ramirez-Montealegre D, Chung M, et al. Juvenile neuronal ceroid lipofuscinosis (JNCL) and the eye. Surv Ophthalmol. 2009 Jul-Aug;54(4):463-71.
  7. Burneo JG, Arnold T, Palmer CA, et al. Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant inheritance in Alabama. Epilepsia.2003;44:841–846.
  8. Chabrol B, Caillaud C, Minassian B. Neuronal ceroid lipofuscinoses. Handb Clin Neurol. 2013;113:1701-6.
  9. Dedelis S. Batten Disease [Internet]. Montreal (QC): Hôpital Sainte-Justine; 2003 [cited 2011 Aug 9]. Available from: http://www.humpath.com/.
  10. Ferrer I, Arbizu T, Peña J, et al. A golgi and ultrastructural study of a dominant form of Kufs’ disease. J. Neurol. 1980;222:183–190.
  11. Frequently Asked Questions [Internet]. U.S. National Human Genome Research Institute National Institutes of Health, [updated 2012 Feb 27; cited 2013 Sept 3]. Available from: http://www.genome.gov/27531963
  12. Hofman IL, van der Wal AC, Dingemans KP, et al. Cardiac pathology in neuronal ceroid lipofuscinoses – a clinicopathologic correlation in three patients. Eur J Paediatr Neurol. 2001;5 Suppl A:213-7.
  13. Josephson SA, Schmidt RE, Millsap P, et al. Autosomal dominant Kufs’ disease: A cause of early onset dementia. J. Neurol. Sci. 2001;188:51–60.
  14. Kirveskari E, Partinen M, Salmi T, et al. Sleep alterations in juvenile neuronal ceroid-lipofuscinosis. Pediatr Neurol. 2000 May;22(5):347-54.
  15. Lamminranta S, Aberg LE, Autti T, et al. Neuropsychological test battery in the follow-up of patients with juvenile neuronal ceroid lipofuscinosis. J Intellect Disabil Res. 2001;45:8-17.
  16. Malcom C, Hain R, Gibson F, et al. Challenging symptoms in children with rare life-limiting conditions: findings from a prospective diary and interview study with families. Acta Paediatr. 2012 Sep;101(9):985-92.
  17. Mole SE, Williams RE. Neuronal Ceroid-Lipofuscinoses [Internet]. GeneReviews;. 2013 Aug 1 [cited 2013 Aug 7]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1428/.
  18. Mole SE, Williams RE, Cooper JD. Special issue: molecular basis of the NCLs. Biochim Biophys Acta. 2013 Nov;1832(11):1793-4.
  19. NCL Resource: A Gateway for Batten Disease [Internet]. London: University College London; Available from: http://www.ucl.ac.uk/ncl.
  20. Nijssen P.C., Brusse E., Leyten AC, et al. Autosomal dominant adult neuronal ceroid lipofuscinosis: Parkinsonism due to both striatal and nigral dysfunction. Mov. Disord. 2002;17:482–487.
  21. Ostergaard JR, Rasmussen TB, Molgaard H, et al. Cardiac involvement in juvenile neuronal ceroid lipofuscinosis (Batten disease). 2011 Apr 5;76(14):1245-51.
  22. Rakheja D, Narayan SB, Bennett MJ. Juvenile neuronal ceroid-lipofuscinosis (Batten disease): a brief review and update. Curr Mol Med. 2007 Sep;7(6):603-608.
  23. Rare Diseases [Internet]. U.S. National Library of Medicine National Institutes of Health; [updated 2013 Aug 8; cited 2013 March 18]. Available from: http://www.nlm.nih.gov/medlineplus/rarediseases.html/.
  24. Rinne JO, Ruottinen HM, Någren K, Aberg LE, Santavuori P. Positron emission tomography shows reduced striatal dopamine D1 but not D2 receptors in juvenile neuronal ceroid lipofuscinosis. Neuropediatrics. 2002 Jun;33(3):138-41.
  25. Sims KB, Cole AJ, Sherman JC, et al. Case records of the Massachusetts General Hospital. Case 8-2011. A 32-year-old woman with seizures and cognitive decline. N. Engl. J. Med. 2011;364:1062–74.
  26. Williams RE, Mole SE. New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology. 2012. Jul 10;79(2):183-191.