Autosomal dominant neuronal ceroid lipofuscinosis 4B

Alternate Names

CLN4B; Kuf's disease, autosomal dominant; Ceroid lipofuscinosis, neuronal, Parry type; Ceroid lipofuscinosis, neuronal, 4B, autosomal dominant; Neuronal ceroid lipofuscinosis 4B; Adult neuronal ceroid lipofuscinosis 4B; Kuf's disease type B; CLN4B disease

Definition

Autosomal dominant neuronal ceroid lipofuscinosis 4B is a form of adult neuronal ceroid lipofuscinosis, which is a rare condition that affects the nervous system.

Onset

Signs and symptoms usually begin around age 30, but they can develop anytime between adolescence and late adulthood.

Epidemiology

CLN4 disease is a rare disorder, but its prevalence is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide.

Cause

It can be caused by changes (mutations) in the DNAJC5 or CTSF gene.

• The DNAJC5 gene provides instructions for making a protein called cysteine string protein alpha (CSPα). This protein is found in the brain, where it plays a role in the transmission of nerve impulses, helping nerve cells communicate with each other. Specifically, CSPα is involved in recycling certain proteins that are involved in nerve impulse transmission by refolding misshapen proteins so that they can be used in additional transmissions.
• DNAJC5 gene mutations lead to the production of an altered CSPα protein. The altered protein cannot perform its function, which reduces protein recycling, causing a shortage (deficiency) of functional proteins needed for impulse transmission. Without normal communication between nerve cells, neurological functions are impaired, contributing to the features of CLN4 disease.
• CLN4 disease, like other NCLs, is characterized by the accumulation of proteins and other substances in lysosomes, which are compartments in the cell that digest and recycle materials. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. The accumulations can cause cell damage leading to cell death. The progressive death of nerve cells in the brain and other tissues contributes to the decline of neurological function in CLN4 disease. However, it is unclear how mutations in the DNAJC5 gene are involved in the buildup of substances in lysosomes.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
• Some cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.

Signs and symptoms

Affected people generally experience behavioral abnormalities, dementia; difficulties with muscle coordination (ataxia); and involuntary movements such as tremors or tics.

Diagnosis

The diagnosis of an NCL is increasingly based on assay of enzyme activity and molecular genetic testing. In unusual cases diagnosis relies on electron microscopy (EM) of biopsied tissues. The diagnostic testing strategy in a proband depends on the age of onset..

Treatment

Treatment options are limited to therapies that can help relieve some of the symptoms.

NIH genetic and rare disease info

• NIH info on Autosomal dominant neuronal ceroid lipofuscinosis 4B

Autosomal dominant neuronal ceroid lipofuscinosis 4B is a rare disease.

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