Systemic hyalinosis: a distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2).
OBJECTIVE
We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.


METHODS
We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis.


RESULTS
We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease.


CONCLUSIONS
Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction.
Shieh
Joseph T C
JT
Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA.
Swidler
Petra
P
Martignetti
John A
JA
Ramirez
Maria Celeste M
MC
Balboni
Imelda
I
Kaplan
Julie
J
Kennedy
Jeanette
J
Abdul-Rahman
Omar
O
Enns
Gregory M
GM
Sandborg
Christy
C
Slavotinek
Anne
A
Hoyme
H Eugene
HE
D017668:Age of Onset; D005260:Female; D006801:Humans; D006818:Hyalin; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D018000:Receptors, Peptide
C447150:ANTXR2 protein, human; D008565:Membrane Proteins; D018000:Receptors, Peptide