CLN10 Disease

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1		Catherine Yang	+ 611 word(s)	611	2020-12-15 07:18:25

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/cln10-disease

CLN10 disease is a severe disorder that primarily affects the nervous system. Individuals with this condition typically show signs and symptoms soon after birth. 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.

genetic conditions

1. Introduction

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.

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.

2. Frequency

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

3. Causes

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).

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.

4. Inheritance

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.

5. Other Names for This Condition

cathepsin D deficiency
cathepsin D deficient neuronal ceroid lipofuscinosis
CLN10
congenital neuronal ceroid lipofuscinosis
neuronal ceroid lipofuscinosis 10
neuronal ceroid lipofuscinosis due to cathepsin D deficiency

References

Anderson GW, Goebel HH, Simonati A. Human pathology in NCL. Biochim BiophysActa. 2013 Nov;1832(11):1807-26. doi: 10.1016/j.bbadis.2012.11.014.
Jalanko A, Braulke T. Neuronal ceroid lipofuscinoses. Biochim Biophys Acta.2009 Apr;1793(4):697-709. doi: 10.1016/j.bbamcr.2008.11.004.Review.
Kousi M, Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinicalcorrelations of over 360 mutations in eight genes that underlie the neuronalceroid lipofuscinoses. Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624.
Siintola E, Partanen S, Strömme P, Haapanen A, Haltia M, Maehlen J, Lehesjoki AE, Tyynelä J. Cathepsin D deficiency underlies congenital human neuronalceroid-lipofuscinosis. Brain. 2006 Jun;129(Pt 6):1438-45.
Steinfeld R, Reinhardt K, Schreiber K, Hillebrand M, Kraetzner R, Bruck W,Saftig P, Gartner J. Cathepsin D deficiency is associated with a humanneurodegenerative disorder. Am J Hum Genet. 2006 Jun;78(6):988-98.
Williams RE, Mole SE. New nomenclature and classification scheme for theneuronal ceroid lipofuscinoses. Neurology. 2012 Jul 10;79(2):183-91. doi:10.1212/WNL.0b013e31825f0547.

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Subjects: Genetics & Heredity

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Catherine Yang

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Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The Gene Associated with CLN10 Disease

4. Inheritance

5. Other Names for This Condition

References