Dysosteosclerosis (DSS), also known as autosomal recessive dysosteosclerosis or X-linked recessive dysosteosclerosis, is a rare osteoclast-poor form of osteosclerosis that is presented during infancy and early childhood, characterized by progressive osteosclerosis and platyspondyly. Platyspondyly and other skeletal abnormalities are radiographic features of the disease which distinguish DSS from other osteosclerotic disorders. Patients usually experience neurological and psychological deterioration, therefore patients are commonly associated with delayed milestones. The cause of DSS is unclear. Different genetic mutations are observed in patients, therefore it is suggested that the cause is genetically heterogeneous. Genetic mutations responsible include, but are not limited to, TCIRG1, TNFRSF11A , and SLC29A3. It is congenital and inherited as an autosomal recessive disorder, however, an X-linked recessive inheritance is outlined in some families. There is no cure for DSS. Supportive care includes orthopaedic care. Symptomatic treatment involves the reduction in calcium intake in diet. Less than 30 cases of DSS have been reported in literature to date. Symptoms and Signs
The main signs and symptoms of DSS includes:
Skeletal abnormalities: platyspondyly, sclerosis
Physical abnormalities: short stature, macrocephaly
Neurological abnormalities: delayed development, mental retardation

Skeletal abnormalities
In general, patients with DSS develop osteopenia and bone fragility. DSS also affects specific areas of the human skeleton, such as the spine, skull, pelvis, and limbs. The most common sign of DSS is platyspondyly, which is the flattening of vertebral bodies of the axial skeleton, present in 80-99% of individuals with DSS.
Some mutant splicing variants would undergo nonsense-mediated mRNA decay (NMD), while others would not be subjected to NMD, and instead produce a truncated isoform of the RANK protein. The mutated protein has structural defects hence hinders normal function in the signalling pathway, contributing to development of the disease. SLC29A3 mutation
The SLC29A3 gene is present in chromosome locus10q22.1, which encodes for the equilibrative nucleoside transporter 3 (ENT3), a nucleoside transporter that is present in membranes of mitochondria and lysosomes. ENT3 is responsible for the trafficking of nucleoside, free purines and pyrimidines into the mitochondria and out of lysosomes. Mutations in the gene is often accompanied by histiocytosis-lymphadenopathy plus syndrome, which is characterised by the accumulation of histiocytes leading to lymphadenopathy and other symptoms.Insertion in the coding region was reported in a patient but no records were found in any genetic databanks. Missense mutation was reported to be present in multiple patients and ranked disease-causing by MutationTaster. This insertion mutation is located in the loop within transmembrane helices 1 and 2, while the missense mutations is located in the loop within transmembrane helix 6, 9, and 11.Mutation leads to impaired ENT3 transportation activity, accumulation of nucleotides and nucleoside in lysosomes. As osteoclasts express the SLC29A3 gene, mutation results in incapacitated differentiated osteoclasts ability in demineralising calcium phosphate crystal surfaces, disrupted osteoclastic differentiation, and diminished osteoclast counts. The reduced osteoclast differentiation and activity results in decreased demineralisation and reabsorption of bone structures.