Osteopetrosis, Autosomal recessive 6 (OPTB6)

(OMIM #611497)

Osteopetrosis, Autosomal recessive 6, is a form of autosomal recessive osteopetrosis (see OPTB1) caused by mutation in the PLEKHM1 (Pleckstrin homology domain-containing protein, family M, member 1) gene. The loss of function mutations in the PLEKHM1 gene underlie an intermediate form of human osteopetrosis.

Gene

PLEKHM1 gene, 17q21.31 (OMIM gene/locus number *611466), encoding a nonsecretory adaptor protein that localizes to endosomal vesicles. A highly truncated Plekhm1 protein has been previously found in a patient with intermediate autosomal recessive osteopetrosis. The exact function of Plekhm1 remains to be determined.

Phenotype

Intermediate form, bone deformities, increased bone density (sclerosis) and generalized high bone mass, pain, chondrolysis, dense metaphyseal bands.

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.

Images

Fig. (a)

Osteopetrosis, Autosomal recessive 6 (OPTB6)

Fig. (b)

Osteopetrosis, Autosomal recessive 6 (OPTB6)

Fig. Radiographies show: (a) cortical sclerosis of the pelvic bones, particularly at the iliac wings. Note the band-like sclerosis of the vertebral endplates (rugger jersey spine) and the inhomo- geneous sclerosis at the metadiaphyses of the distal femora, tibiae and fibulae, and proximal fibulae and tibiae. Also note the broadening of the involved segments of the long bones (“Erlenmeyer flask” deformity). (b) Radiograph of the right femur showing the presence of a dense metaphyseal band at the distal metaphysis.

Reproduced from Van Wesenbeeck L, Odgren PR, Coxon FP, et al., Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. J Clin Invest 2007;117:919-30.

Other resource

Osteopetrosis Society (OPETS)

References
  1. Van Wesenbeeck L, Odgren PR, Coxon FP, et al. Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. J Clin Invest. 2007 Apr;117(4):919-30.
  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