CLN10, disease ... (CLN10 disease) - Gen CTSD
The CLN10 disease, also known as cathepsin D deficiency or neuronal ceroid ceroidal congenital, is a serious process that primarily affects the nervous system. Affected individuals usually show signs and symptoms shortly after birth. These signs and symptoms may include muscle rigidity, respiratory distress and seizures. In addition, it is likely that some people affected also suffer from seizures before birth during intrauterine development. Infants with the disease have CLN10 microcephaly with brain which may be less than half the normal size. There is a loss of brain cells in the cerebellum and cerebral cortex. Brain nerve cells also lack myelin. Often, infants with the disease die CLN10 hours or weeks after birth.
In some individuals with CLN10 disease, the condition does not appear until later in life, between late childhood and adulthood. These individuals have a gradual loss of brain cells and often develop ataxia, loss of speech, cognitive impairment and vision loss. Individuals with late - onset form have a reduced life expectancy, which can vary depending on the age of onset of signs and symptoms.
This process is due to mutations in the CTSD gene (cathepsin D), located on the short arm of chromosome 11 (11p15.5), encoding cathepsin D. Cathepsin D is one of a family of proteins that act as cathepsin protease enzymes which modify proteins to separate. Cathepsin D is found in many cell types and is active in the lysosomes. When cleaves proteins, cathepsin D can break down certain proteins, other proteins activate and regulate apoptosis. Cathepsin D is synthesized as an inactive enzyme called preproenzyme having additional segments linked protein. These segments must be removed, followed by additional processing steps, so that the enzyme is active. Cathepsin D mature active consists of two parts, a light chain and a heavy chain.
It has identified at least 7 CTSD gene mutations in individuals with CLN10 disease. The CTSD genetic mutations that lead to the disease CLN10 and are present at birth inhibit the enzymatic activity of cathepsin D. As a result, proteins and fats are broken down properly and accumulate abnormally inside lysosomes. As these substances accumulate in cells throughout the body, nerve cells seem to be particularly vulnerable to damage caused by abnormal cellular materials. Early and widespread loss of nerve cells in the CLN10 disease results in severe signs and symptoms and death in childhood. It is likely that cases of late - onset disease, CTSD gene mutations result in the synthesis of a cathepsin D 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 than these substances accumulate in the lysosomes and cause death of nerve cells.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with disease CLN10 by the complete PCR amplification of the exons of the CTSD gene and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).