About TGM1-deficient ARCI
About TGM1-deficient ARCI
Autosomal Recessive Congenital Ichthyosis, or ARCI, is a lifelong, severe genetic skin disease. While a number of genetic mutations have been associated with the development of ARCI, the most common cause of ARCI is an inactivating mutation in the TGM1 gene encoding the enzyme transglutaminase-1, a protein that is essential for the proper formation of the skin barrier. Mutations in the TGM1 gene, and the subsequent disruption to the epidermal barrier, lead to pronounced dehydration, transepidermal exposure to unwanted toxins and surface microorganisms, and a greatly increased risk of infection. Transglutaminase-1 deficiency is associated with increased mortality in the neonatal period and has a dramatic impact on quality of life.
Patients suffering from ARCI often exhibit life-long pronounced scaling of the skin with increased transepidermal water loss (TEWL). The scales are plate-like, often of a dark color, and can cover the whole body. Such patients frequently suffer from exposure of the inner eyelid surface due to turning away of the eyelids from the eye (ectropion), the turning outwards of the lips (eclabium), deformities of joint and nasal cartilage (hypoplasia), scarring alopecia, especially at the edge of the scalp, and a thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Additional complications experienced by ARCI patients include episodes of sepsis, fluid and electrolyte imbalances due to impaired skin barrier function, and failure to thrive, especially during the neonatal period and infancy. Severe heat intolerance and nail dystrophy are also frequently observed. No effective medication is available to treat this severe disease; current therapies only relieve some symptoms. Our second product, KB105, is currently the subject of an ongoing phase I/II clinical trial for the treatment of TGM1-deficient ARCI.
For more information on autosomal recessive congenital ichthyosis, visit:
Foundation for Ichthyosis & Related Skin Types: http://www.firstskinfoundation.org/
