BioCystinosis – Biomarker for Cystinosis Disease
Cystinosis is a rare, multisystem genetic disorder characterized by the accumulation of an amino acid called cystine in different tissues and organs of the body including the kidneys, eyes, muscles, liver, pancreas and brain. Generally, cystinosis is broken down into three different forms known as nephropathic cystinosis, intermediate cystinosis and non-nephropathic (or ocular) cystinosis. Nephropathic cystinosis presents in infancy and is the most common and severe form. Early detection and prompt treatment are criticalin slowing the development and progression of symptoms associated with cystinosis. The kidneys and eyes are the two organs most often affected. Individuals with nephro-pathic or intermediate cystinosis ultimately require a kidney transplant. Non-nephropathic cystinosis only affects the corneas of the eyes. Cystinosis is caused by mutations of the CTNS gene and is inherited as an autosomal recessive disease.
The specific symptoms and severity of cystinosis vary greatly from one person to another based upon several factors including age of onset and whether the disorder is promptly diagnosed and treated. The progression of the disorder can be slowed by early diagnosis and treatment. Eventually, cystinosis can affect all tissues of the body. The age of onset for different symptoms varies greatly.
There are various different forms of Cystinosis:
NEPHROPATHIC CYSTINOSIS (renal Fanconi disease)
Nephropathic cystinosis is the most frequent and most severe form of cystinosis. The symptoms of nephropathic cystinosis usually become apparent within the second half of the first year of life. Specific symptoms can be mild or severe based upon each individual case and the age when treatment is started.Growth failure and renal Fanconi disease are usually the first noticeable complications of the disorder. Although infants appear normal at birth, by the age of one they often fall into the third percentile for height and weight. In addition, affected infants may have episodes of vomiting, poor appetite, and feeding difficulties that contribute (along with kidney dysfunction) to nutritional deficiency and the failure to gain weight and grow at the expected rate (failure to thrive). Ultimately, growth in untreated children with cystinosis occurs at 60 percent the expected rate.
Infants with nephropathic cystinosis develop renal Fanconi disease, a rare disorder characterized by kidney dysfunction. The kidney tubules fail to reabsorb a variety of needed substances, including the compounds mentioned above as well as amino acids, phosphate, calcium, glucose, carnitine, certain proteins and electrolytes. Consequently, affected individuals have abnormally low levels of many of these substances in the body.
Also known as nephropathic juvenile cystinosis or adolescent cystinosis, this form of cystinosis is characterized by all of the signs and symptoms of nephropathic cystinosis described above. However, onset of these symptoms does not occur until later perhaps around 8 years of age. Generally, the symptoms are less severe than in the classical infantile nephropathic form and have a slower progression. If untreated, endstage renal failure in intermediate cystinosis usually develops at some point between 15 and 25 years of age. There is a spectrum of disease severity in cystinosis, with overlap of the infantile and intermediate forms.
Also known as ocular or "benign" cystinosis, this form usually affects adult's during middle age; it was once called adult cystinosis. Kidney disease does not occur in these individuals. The disorder appears to only affect the eyes. Untreated individuals with non-nephropathic cystinosis eventually develop photophobia due to cystine crystal accumulation in the eyes.New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to identify and validate a new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.