Adult Neuronal Ceroid Lipofuscinosis

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

CLN6, TPP1, CLN3, ATP13A2, CLCN3, CLCN6, CLN5, CTSD, CLN8, PPT1, MFSD8, CTSF, PSEN1, DNAJC5, SCARB2, NCL

Drugs

Adeno-associated viral vector serotype 9 containing the human CLN1 gene, Brivaracetam, Gemfibrozil

Adeno-associated viral vector serotype 9 containing the human CLN1 gene, Brivaracetam, Gemfibrozil, Recombinant self-complementary adeno-associated viral vector serotype 9 containing the human CLN3 gene, recombinant self-complementary adeno-associated viral vector serotype 9 (AAV9) containing the human CLN3 gene, recombinant self-complementary adeno-associated viral vector serotype 9 containing the human CLN6 gene

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A genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs) with onset during the third decade of life, characterized by dementia, seizures and loss of motor capacities, and sometimes associated with visual loss caused by retinal degeneration.

Epidemiology

Prevalence is unknown.

Clinical description

The clinical picture is characterized by onset with progressive myoclonic epilepsy or behavioral disturbances, dementia and extrapyramidal motor symptoms that appear at the age of 20-30 years. Vision loss is an uncommon feature and depends on the underlying genetic cause.

Etiology

The ANCL phenotype was originally designated as CLN4 disease, although the causative gene has not yet been identified. CLN4 may be inherited in an autosomal recessive (CLN4A) or autosomal dominant (CLN4B) manner. In addition, autosomal recessive ANCL may be caused by mutations in the following genes PPT1 (1p32; designated CLN1 and responsible for ANCL with vision loss) and CTSD (designated CLN10; 11p15.5).

Diagnostic methods

The diagnosis is based on the clinical picture, and enzymatic analysis (to detect deficiencies in palmitoyl-protein thioesterase 1 and cathepsin D, present in patients with PPT1 and CTSD mutations, respectively) and molecular testing. For some types, demonstration of storage material in tissues by electron microscopy is necessary for diagnosis.

Differential diagnosis

The differential diagnosis should include progressive myoclonus epilepsies (Unverricht-Lundborg disease, Lafora disease and MERRF syndrome), Ramsay-Hunt syndrome and late manifesting forms of several other lysosomal storage disorders (GM2 gangliosidosis, Gaucher disease and Niemann-Pick type C disease; see these terms).

Antenatal diagnosis

Prenatal diagnosis is feasible for families in which the disease causing mutation has been identified.

Genetic counseling

Genetic counseling should be proposed.

Management and treatment

Management is supportive only.

Prognosis

ANCLs follow a slowly progressive course with possible survival to the fifth decade.