Neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinoses (NCLs), occasionally known collectively as Batten disease, are a group of genetic neurodegenerative disorders of childhood in which there is excessive accumulation of lipofuscin.

Terminology

The use of Batten disease as an umbrella term for neuronal ceroid lipofuscinoses is somewhat problematic, as the eponym is also variably used to specifically describe the CLN3 variant.

Clinical presentation

Clinical presentation is heterogeneous as is onset, which renders the diagnosis hard to make. Skin punch biopsy can reveal abnormality typical of the disease ².

MR brain volumetry has been shown to correlate well with disease progression, more so than current clinical disease scores ³.

Pathology

The group includes at least fourteen entities, and are classified by the underlying genetic abnormality. This supersedes previous classifications which relied on clinical features (e.g. onset of disease) and other non-genetic features, resulting in a number of eponymously named entities ⁶.

• CLN1: PPT1 gene

  • previously Haltia-Santavuori disease

• CLN2: TPP1 gene

  • previously Jansky-Bielschowsky disease

• CLN3: CLN3 gene

  • previously Batten-Spielmeyer-Vogt disease (or Batten disease)

• CLN4: DNAJC5 gene

  • previously Parry disorder

• CLN5: CLN5 gene

• CLN6: CLN6 gene

  • one of the disorders previously known as Kufs disease

• CLN7: MFSD8 gene

• CLN8: CLN8 gene

• CLN9: CLN9 gene

• CLN10: CTSD gene

• CLN11: GRN gene

• CLN12: ATP13A2 gene

• CLN13: CTSF gene

  • one of the disorders previously known as Kufs disease

• CLN14: KCTD7 gene

Radiographic features

Radiographic features are non-specific and include mainly generalized brain atrophy and white matter changes probably induced by Wallerian degeneration and gliosis ². Brain atrophy can be extreme with end stage disease, associated with diffuse (complete) white matter changes ². Cerebellar atrophy tends to be significant.

MRI

• T2/FLAIR:

  • non-specific hyperintense white matter changes

    • at the extreme of the spectrum, the white matter can appear more hyperintense than the grey matter ⁴

  • infantile subtypes:

    • thin hyperintense periventricular bands

  • late infantile subtypes:

    • hypointense thalami (late infantile subtypes) or basal ganglia

• spectroscopy:

  • reduced NAA

  • elevated mobile lipids (ML) on protonic spectroscopy

Treatment and prognosis

Management is generally supportive. However, for CLN2, enzyme replacement is available through cerliponase alfa, which is a recombinant form of the enzyme deficient in this condition (tripeptidyl peptidase) and is delivered via the intraventricular route ⁵.