Osteopetrosis, Autosomal recessive 5 (OPTB5)

(OMIM phenotype number #259720)

Osteopetrosis, Autosomal recessive 5, is a form of autosomal recessive osteopetrosis (see OPTB1) caused by mutation in the gene encoding osteopetrosis-associated transmembrane protein-1 (OSTM1 gene). Mutations in OSTM1 entail the most severe form of autosomal recessive osteopetrosis. This disease is characterized by a very severe clinical presentation poor prognosis, with a severe central nervous system involvement, whose predominant symptoms are marked cerebral atrophy and a decreased myelinization, in addition to the classical severe bone sclerosis.


OSTM1 gene, 6q21 (OMIM gene/locus number #607649), encoding Osteopetrosis-associated transmembrane protein 1, required for osteoclasts maturation and function.


Severe form, loss of trabecular structure, poor/no definition between cortical and medullary bone, fractures, increased bone density (sclerosis) and generalized high bone mass, in utero fractures, and skeletal hyperdensity, hepatosplenomegaly, hydrocephaly, microcephaly, cerebral atrophy, visual impairment, and bone marrow insufficiency.

Main biochemical alterations

Adult/intermediate forms: high CK-BB, high bone ALP. Infantile/severe forms: low Ca, high PTH, high 1,25(OH)2D, high CK-BB, high AP, anemia.


a   b

Fig. Radiographies show: (a) femur and tibia lack bone marrow cavities and the translucent growth plate at the distal femur seems irregular, (b) typical sandwich appearance of vertebrae dur to endplate sclerosis.

Reproduced from Bone, Vol 55, Ott CE, Fischer B, Schröter P, et al. Severe neuronopathic autosomal recessive osteopetrosis due to homozygous deletions affecting OSTM1, Pages 292-7, Copyright 2013, with permission from Elsevier.

Other resource:



  1. Pangrazio A, Poliani PL, Megarbane A, et al. Mutations in OSTM1 (grey lethal) define a particularly severe form of autosomal recessive osteopetrosis with neural involvement. J Bone Miner Res. 2006 Jul;21(7):1098-105.
  2. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  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