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  • Updated 04.29.2024
  • Released 02.17.1994
  • Expires For CME 04.29.2027

Batten disease



Batten disease, or neuronal ceroid lipofuscinosis, constitutes one of the most common groups of inherited childhood-onset neurodegenerative disorders. They currently comprise 13 genetically distinct disorders that differ by causative gene, gene product, and biological process. Neuronal ceroid lipofuscinoses share disease features, including vision loss, epilepsy, cognitive decline, and movement disorders with onset in childhood, adolescence, and even adulthood. Abnormal autofluorescent, electron-dense granules accumulate in the cytoplasm of nerve cells and are associated with selective destruction and loss of neurons in the brain and retina. There are currently 13 different genes and over 360 mutations that underlie these devastating brain disorders. CNS-targeted enzyme replacement therapy is approved for one form of disease: neuronal ceroid lipofuscinosis type 2 (CLN2) disease.

Key points

• Neuronal ceroid lipofuscinoses, or Batten disease, are common causes of neurodegeneration in childhood.

• Typical clinical findings include retinopathy leading to blindness, sleep problems, movement disorders, epilepsy, dementia, and premature death.

• Definitive diagnosis relies on enzymatic assays or DNA testing.

• Intraventricular cerliponase alfa for ceroid lipofuscinosis type 2 disease is the first and only FDA- and EMA-approved therapy for a specific form of neuronal ceroid lipofuscinosis (CLN2 disease).

• Kufs disease or adult neuronal ceroid lipofuscinosis can be caused by three different genes and is often misdiagnosed pathologically.

Historical note and terminology

A detailed history of the classification and the pathological and clinical characteristics has been reviewed (29). Neuronal ceroid lipofuscinosis consists of a group of genetically determined neurodegenerative disorders that affect children and adults of both sexes. The original description of the disorder is credited to Stengel, a Danish physician, who identified four children in a family from a rural village in Norway who had onset of visual failure in their sixth year, followed by progressive intellectual decline and loss of speech. Seizures began at 10 years, and they died in their twenties after remaining in a vegetative state for several years (65).

The visual loss and dementia noted in this disease led to its classification as a form of amaurotic familial idiocy, but an appreciation of the pathological differences, biochemical abnormalities, and genetic defects have established neuronal ceroid lipofuscinosis as a nosologic entity. The eponym Batten disease, now often associated with the juvenile form of the disease or CLN3 disease, is named for Frederick Batten, who, in 1903, described the cerebral and macular changes in two brothers (07). Subsequently, Purkinje cells, gliosis, and the loss of cortical neurons in association with the pathognomonic accumulation of the autofluorescent lipopigments in the remaining neurons were documented and helped to distinguish Batten disease from other syndromes associated with intellectual disability (73; 10; 08). Although the clinical features of the juvenile onset form were delineated in great detail (64; 61), the adult variant was not recognized until 1925 (40). The high prevalence of an infantile onset form of Batten disease in Finland was later identified (57), thereby uncovering the clinical spectrum of neuronal ceroid lipofuscinosis. Other subtypes, such as a variant of late infantile neuronal ceroid lipofuscinosis and a congenital form have been described (41; 22). Advances in molecular genetics have led to the discovery of the gene defects for several of the variants (47). The genetics of this group of disorders demonstrates that they are heterogeneous disorders with common pathologic and clinical features (See Table 1). Neuronal ceroid lipofuscinoses were initially classified by the age at disease onset (eg, infantile, late infantile, juvenile, adult). However, genetic advances have demonstrated that many cases may not follow this strict classification. For example, CLN1 disease patients with juvenile disease onset have been described. Therefore, disease classification based on affected gene is now favored.

Table 1. Genetic Information of Neuronal Ceroid Lipofuscinosis Variants

Gene Name

Gene Product

Type of Product

Typical Age at Onset


Palmitoyl protein thioesterase (PPT1)




Tripeptidyl peptidase (TPP1)


Late infantile



Transmembrane protein, lysosomal



DNAJ heat shock protein family (Hsp40) member C5 (DNAJC5)

Cysteine string protein




Soluble lysosomal protein

Late infantile



Transmembrane, ER

Late infantile


Major facilitator superfamily domain containing 8 (MFSD8)

Transmembrane, lysosomal

Late infantile



Transmembrane, ER

Late infantile


Cathepsin D (CTSD)




Granulin precursor (GRN)

Soluble cofactor protein



ATPase cation transporting 13A2 (ATP13A2)

Transmembrane protein



Cathepsin F (CTSF)




Potassium channel tetramerization domain containing 7 (KCTD7)


Late infantile

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