Infantile Systemic Hyalinosis (ISH) is a very rare autosomal recessive disorder characterized by connective tissue involvement as hyaline deposition in skin, gastrointestinal tract, muscles, glands and other organs.We report eight Iranian children (4 male and 4 female) with ISH referred to our hospital from 1996 to 2013. The illness had been diagnosed by clinical manifestations and disease progression. Six of them died and two are alive but very sick.ISH is a very rare disorder with poor prognosis. Seventy five percent of our 8 patients died before 2 years old due to severe diarrhea, malabsorption and/or infection.