Cystinosis is a rare, inherited metabolic disorder characterized by the abnormal accumulation of the amino acid cystine within the lysosomes of cells throughout the body. This accumulation occurs due to a genetic mutation that impairs the transport of cystine out of these cellular compartments. Over time, the excess cystine forms crystals, which slowly damage various organs and tissues. This progressive damage results in a range of visible signs and symptoms that can change as the disease advances.
Early Childhood Visible Symptoms
In infants and young children, particularly with the most common form, infantile nephropathic cystinosis, initial physical signs often emerge between 6 and 18 months of age. A primary visible indicator is “failure to thrive,” which includes poor weight gain and overall stunted growth. Affected children may appear noticeably smaller than their peers, often falling below the third percentile for height and weight by their first birthday.
Visible signs related to Fanconi syndrome, a kidney complication, are also common. These can manifest as dehydration, with noticeable symptoms such as dry skin, sunken eyes, and excessive thirst leading to frequent fluid intake and urination. Early, subtle indications of rickets, a bone-softening condition, might also be observed, including general bone softness and initial signs of leg bowing or widening of the wrists and ankles. Children may also show visible distress from symptoms like frequent vomiting or constipation.
Ocular Manifestations
The eyes are frequently and prominently affected in cystinosis, often serving as a diagnostic feature. Cystine crystals accumulate in the cornea and conjunctiva, the clear front surface and the membrane lining the eyelid, respectively. These crystals appear as small, shiny, needle-like formations, often white or iridescent, and can be visible to the naked eye in older, untreated patients or through specialized examination with a slit lamp as early as 12 to 18 months of age.
The presence of these crystals can lead to associated visible symptoms, such as photophobia, an extreme sensitivity to light. This manifests as frequent squinting, visible discomfort in bright environments, or an avoidance of light altogether, sometimes requiring patients to wear dark glasses even indoors. Visible irritation or redness of the eyes might also occur due to the crystal accumulation.
Skeletal and Growth-Related Appearances
As cystinosis progresses, more pronounced and long-term physical changes affect the overall body structure and growth. Severe short stature, sometimes described as dwarfism, becomes a characteristic and significant physical feature. Children with cystinosis typically experience reduced growth velocity, with average growth rates around 60% of what is expected without adequate treatment.
Chronic rickets, resulting from the kidney’s inability to reabsorb phosphate, leads to specific skeletal deformities. These can include pronounced bowed legs (genu varum) or knock-knees (genu valgum), widening of the wrists and ankles, and potentially spinal curvatures. Muscle wasting and generalized weakness also contribute to a visibly frail appearance, with thin limbs that can affect posture or gait, making walking painful enough to delay ambulation.
Systemic Manifestations and Disease Progression
As the disease advances and affects multiple organ systems, broader physical changes become apparent. Visible signs related to kidney involvement, beyond the initial Fanconi syndrome, include pallor or paleness of the skin due to anemia in later stages of kidney failure. Edema, or swelling, particularly in the face, hands, or lower extremities, can also occur due to fluid retention.
Visible signs of hypothyroidism, which can develop as the thyroid gland is affected, might include a puffy face, dry skin, sparse or brittle hair, and a generally lethargic demeanor that impacts overall appearance. Other less common but visible signs contributing to the overall physical presentation can emerge, such as difficulties with swallowing that may affect facial muscle movement or eating habits. Neurological signs impacting coordination or gait can also lead to a more distinct or frail appearance in advanced stages. The overall physical appearance of a person with cystinosis can become progressively more affected and distinct as the disease advances without appropriate treatment.