Cystinoses

Cystinosis Cystinosis is a rare, inherited metabolic disorder characterized by the abnormal accumulation of the amino acid cystine within cells. This accumulation leads to the formation of crystals that can cause damage to various organs and tissues, particularly the kidneys and eyes.

Pathophysiology

Cystinosis is caused by mutations in the CTNS gene, which encodes the protein cystinosin. Cystinosin is responsible for transporting cystine out of lysosomes. When this transport is impaired, cystine accumulates within lysosomes, forming crystals that can disrupt cellular function.

Lysosomal Storage Disorders

Cystinosis is classified as a lysosomal storage disorder, a group of diseases characterized by the accumulation of substances within lysosomes due to defective lysosomal function.

Types of Cystinosis

There are three main types of cystinosis, classified based on the age of onset and severity of symptoms: 1. Nephropathic Cystinosis: This is the most common and severe form, usually presenting in infancy. It is characterized by renal tubular Fanconi syndrome, growth retardation, and progressive kidney failure. 2. Intermediate Cystinosis: Symptoms appear in late childhood or adolescence. It is less severe than nephropathic cystinosis but can still lead to kidney damage. 3. Non-nephropathic (Ocular) Cystinosis: This form primarily affects the eyes, causing photophobia due to cystine crystal accumulation in the cornea.

Symptoms

• Renal Symptoms: Polyuria, polydipsia, and renal tubular Fanconi syndrome are common in nephropathic cystinosis.
• Growth Retardation: Due to metabolic imbalances and kidney dysfunction.
• Ocular Symptoms: Photophobia and corneal deposits are common in all forms.
• Endocrine Disorders: Hypothyroidism and diabetes mellitus can occur in later stages.

Diagnosis

Diagnosis of cystinosis is based on clinical symptoms, family history, and laboratory tests. Measurement of cystine levels in leukocytes is a definitive diagnostic test. Genetic testing can confirm mutations in the CTNS gene.

Treatment

The primary treatment for cystinosis is cysteamine, a medication that reduces cystine accumulation by converting it to cysteine and a cysteine-cysteamine mixed disulfide, which can exit the lysosome.

• Cysteamine Therapy

Cysteamine therapy is crucial for managing cystinosis and preventing organ damage. It is available in oral and ophthalmic formulations.

Prognosis

With early diagnosis and treatment, individuals with cystinosis can have improved outcomes and quality of life. However, kidney transplantation may be necessary as the disease progresses.

Research and Future Directions

Ongoing research aims to improve treatment options, including gene therapy and novel drug formulations. Understanding the molecular mechanisms of cystinosis may lead to better therapeutic strategies.

See Also

• Lysosomal Storage Disorders
• Cysteamine Therapy
• Renal Tubular Fanconi Syndrome

NIH genetic and rare disease info

• NIH info on Cystinoses

Cystinoses is a rare disease.