Infantile systemic hyalinosis: A clinicopathological study

Abstract

Infantile systemic hyalinosis (ISH) is a presumed autosomal recessive connective tissue condition. Symptoms usually begin at birth or shortly thereafter, and are characterized by pain when handled, painful and swollen joints and, later on, dermal anomalies, diarrhea, failure to thrive and recurrent infections, which usually lead to death around the age of 2. The skin has generally diminished elasticity with small pearly papules appearing on neck, ears, coccygeal region, and face. We present two unrelated patients with ISH, with specific focus on clinical and pathologic studies. In the first patient the diagnosis was made several years after she died, in a retrospective study of her clinical file. On ultrastructural examination both patients showed an accumulation of fibrillogranular material in the extracellular matrix with long-spacing collagen of 90 nm. The first child died at the age of 1(1/2) years and the second at 3 years.

Systemic hyalinosis mutations in the CMG2 ectodomain leading to loss of function through retention in the endoplasmic reticulum

“…It is characterized by the accumulation of amorphous, unidentified hyaline material in the skin and other organs [Fayad et al, 1987;Keser et al, 1999;Landing and Nadorra, 1986] leading to papulonodular skin lesions, gingival hypertrophy, flexion contractures of the joints, large subcutaneous tumors commonly involving the scalp, and osteolytic lesions of the long bones, skull, and distal phalanges [Fayad et al, 1987;Keser et al, 1999] (see also www.orpha.net). Infantile systemic hyalinosis (ISH; MIM] 236490), the most severe form of the disease, leads to death in early childhood, mainly due to severe diarrhea, recurrent infections, and failure to thrive [Criado et al, 2004;Landing and Nadorra, 1986]. Patients afflicted with the milder form of the disease, juvenile hyaline fibromatosis (JHF; MIM] 228600), usually live beyond adolescence.…”

Infantile systemic hyalinosis: Case report and review of the literature

“…10 Since that time, 34 additional cases have been reported, including a recent review of 19 cases from a referral center in Saudi Arabia. 1,9,11,12,17,23,24 Although ISH is panethnic, it is noted that many cases reported have been of MiddleEastern origin. 1,2,12,15,25 While some of the presumed increased incidence among this population may be attributed to a higher rate of consanguineous relationships, Al-Mayouf et al 2 have suggested a higher underlying carrier frequency in this population.…”

“…J AM ACAD DERMATOL VOLUME 58, NUMBER 2 Histologic evaluation of the skin and organ biopsy specimens demonstrated deposits of amorphous hyaline material in the dermis and viscera. 17 The nature of the hyaline material remains unclear 11 ; however, some studies have observed an ultrastructural fibrillogranular material with a banding pattern identical to type VI collagen, a normal dermal component. 12,18 Hyaline deposits in the gastrointestinal tract may lead to diarrhea and protein-losing enteropathy.…”

“…Other less commonly reported features of ISH include the reduction of fetal movements, rigidity of the spine, joint swelling, protein losing enteropathy, edema, recurrent vomiting, saddle nose deformity, sunken eyes, and pathologic fractures. 2,[9][10][11][12][13] Of these features, our patient demonstrated protein losing enteropathy, edema, a widened nasal bridge, and sunken eyes. Our patient demonstrated ageappropriate social and language developmental milestones, although physical development was delayed, likely because of painful joint contractures.…”

Infantile Systemic Hyalinosis: A Case Report of Compromised Cellular and Humoral Branches of the Immune System Leading to Infections

“…This syndrome was first described by Nezelof in 1978, and numerous cases have subsequently been documented in the literature. ISH presents with increasing contractures, joint pain, thickened skin, and perianal papules typically within the first 6 months of life 1,4,5. A protein losing enteropathy (PLE) with resultant diarrhea and failure to thrive has been associated with ISH 1,2,4,6.…”