Neuronal ceroid lipofuscinosis 10

Alternate names

CLN10; Ceroid lipofuscinosis neuronal Cathepsin D-deficient; Neuronal ceroid lipofuscinosis due to Cathepsin D deficiency; CLN10 disease, congenital (subtype); CLN10 disease, late infantile (subtype); CLN10 disease, juvenile (subtype); CLN10 disease, adult (subtype); Cathepsin D deficiency

Definition

Neuronal ceroid lipofuscinosis 10 (CLN10 disease) is a type of neuronal ceroid lipofuscinosis (NCL), a group of severe diseases that affect the nervous system.

Summary

• CLN10 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). All of these disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability.
• The different NCLs are distinguished by their genetic cause.
• Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.

Epidemiology

The prevalence of CLN10 disease is unknown; at least 11 cases have been described.

Cause

Mutations in the CTSD gene cause CLN10 disease. The CTSD gene provides instructions for making an enzyme called cathepsin D. Cathepsin D is one of a family of cathepsin proteins that act as protease enzymes, which modify proteins by cutting them apart. Cathepsin D is found in many types of cells and is active in lysosomes, which are compartments within cells that digest and recycle different types of molecules. By cutting proteins apart, cathepsin D can break down certain proteins, turn on (activate) other proteins, and regulate self-destruction of the cell (apoptosis).

Gene mutations

• CTSD gene mutations found to cause CLN10 disease that is present at birth lead to a complete lack of cathepsin D enzyme activity.
• As a result, proteins and fats are not broken down properly and abnormally accumulate within lysosomes.
• While accumulations of these substances occurs in cells throughout the body, nerve cells appear to be particularly vulnerable to damage caused by the abnormal cell materials. Early and widespread loss of nerve cells in CLN10 disease leads to severe signs and symptoms and death in infancy.
• In the later-onset cases of CLN10 disease, CTSD gene mutations likely result in the production of a cathepsin D enzyme whose function is greatly reduced but not eliminated.
• As a result, some proteins and fats are broken down by the enzyme, so it takes longer for these substances to accumulate in lysosomes and cause nerve cell death.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Onset

Signs and symptoms of CLN10 usually appear soon after birth. In some cases, people with CLN10 disease do not develop symptoms until later in infancy, childhood, or adulthood.

Signs and symptoms

• These signs and symptoms can include muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus).
• It is likely that some affected individuals also have seizures before birth while in the womb. Infants with CLN10 disease have unusually small heads (microcephaly) with brains that may be less than half the normal size.
• There is a loss of brain cells in areas that coordinate movement (the cerebellum) and control thinking and emotions (the cerebral cortex).
• Nerve cells in the brain also lack a fatty substance called myelin, which protects them and promotes efficient transmission of nerve impulses. Infants with CLN10 disease often die hours to weeks after birth.
• In some individuals with CLN10 disease, the condition does not appear until later in life, between late infancy and adulthood. These individuals have a gradual loss of brain cells and often develop problems with balance and coordination (ataxia), loss of speech, a progressive loss in intellectual functioning (cognitive decline), and vision loss.
• Individuals with later-onset CLN10 disease have a shortened lifespan, depending on when their signs and symptoms first started.

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 is currently symptomatic and palliative only.
• Seizures, malnutrition, gastroesophageal reflux, pneumonia, sialorrhea, depression and anxiety, spasticity, Parkinsonian symptoms, and dystonia can be effectively managed.
• Antiepileptic drugs (AEDs) should be selected with caution.
• Benzodiazepines may help control seizures, anxiety, and spasticity.
• Trihexyphenydate may improve dystonia and sialorrhea.
• Individuals with swallowing problems may benefit from placement of a gastric (G) tube.Mole SE, Williams RE. Neuronal Ceroid-Lipofuscinoses – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2001 Oct 10 [Updated 2013 Aug 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1428/</ref>[1].

NIH genetic and rare disease info

• NIH info on Neuronal ceroid lipofuscinosis 10

Neuronal ceroid lipofuscinosis 10 is a rare disease.

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