Dysosteosclerosis (DSS)

(OMIM phenotype number %224300)

Dysosteosclerosis is an extremely rare form of osteopetrosis, presents in infancy or early childhood, with a poor prognosis. The disease is characterized by diffuse osteosclerosis, red-violet macular atrophy, platyspondyly and metaphyseal osteosclerosis with relative radiolucency of widened diaphyses. Bone histology during childhood shows unresorbed primary spongiosa and a paucity of osteoclasts when the disease presents. Most cases of DSS appear to be inherited in an autosomal recessive fashion, though X-linked recessive inheritance has been proposed in one family. Fewer than 25 cases have been reported since the first description by Ellis in 1934.

Gene

SLC29A3 gene, 10q22.1 (OMIM gene/locus number #612373). This gene encodes a nucleoside transporter.

Phenotype

Platyspondyly and metaphyseal osteosclerosis with relative radiolucency of widened diaphyses, dense but brittle skeleton, short stature and fractures, optic atrophy and sometimes cranial nerve palsy, failure of tooth eruption, developmental delay, seizures, skin findings such as red-violet macular atrophy, and at the histopathological level paucity of osteoclasts.

Main biochemical alterations

Low total and bone ALP, low TRAP5b, low Ur DPD/Cr.

References

  1. Whyte MP, Wenkert D, McAlister WH. Dysosteosclerosis presents as an "osteoclast-poor" form of osteopetrosis: comprehensive investigation of a 3-year-old girl and literature review. J Bone Miner Res. 2010 Nov;25(11):2527-39.
  2. Campeau PM, Lu JT, Sule G, et al. Whole-exome sequencing identifies mutations in the nucleoside transporter gene SLC29A3 in dysosteosclerosis, a form of osteopetrosis. Hum Mol Genet. 2012 Nov 15;21(22):4904-9.
  3. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  4. http://www.omim.org