Biomarker for Cystinosis Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

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. Early detection and prompt treatment are critical in slowing the development and progression of symptoms associated with Cystinosis. The kidneys and eyes are the two organs most often affected. Individuals with nephropathic 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.

• 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.

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.