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Dante Labs US Report

Osteoarthritis and rare cartilage diseases Report

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The term osteoarthritis (OA) indicates a complex and heterogeneous set of pathological conditions affecting bones and cartilages. It is the most widespread musculoskeletal disease in the world, with a multifactorial etiology and able of affecting any joint, although the anatomical sites most affected are the hands, hips and knees. The main signs and symptoms of OA include pain, stiffness, reduction/loss of joint mobility and stability, swelling and muscle weakness.
OA generally begins late in life as a result of the mixture of genetic and environmental factors, although there are some very rare types of osteoarthritis (and associated conditions) that are configured as monogenic disorders with early-onset and rapidly disabling.
This is an area of ​​study that has not yet been explored but may contribute to a greater clinical understanding of OA.
Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is an autosomal recessive disease affecting tendons and bones, with pleural and pericardial involvement. It is characterized by hip deformity (called coxa-vara), camptodactyly and arthropathy. The genetic defect responsible for its onset affects a lubricating protein (lubricin), present in the synovial fluid but also in the lungs, heart and liver.
Chondrodysplasias are a group of inherited disorders characterized by deformities and abnormalities in skeletal development, as well as by early OA. Rare and phenotypically severe, chondrodysplasias are divided into various subtypes including the acromesomelic form, which in turn includes the Hunter-Thompson type and the Grebe type, both with autosomal recessive inheritance.
Pseudoachondroplasia is another skeletal developmental disorder that occurs around the age of two, typically resulting in short stature, difficulty walking, and joint laxity, among other symptoms.
In Multiple Epiphyseal Dysplasia, skeletal changes mainly affect the ends of the long bones, called epiphesis. There are forms with dominant transmission (which occur in infancy) and recessive transmission (with later onset), but in both cases the failure of the correct development of cartilage prevents physiological bone growth causing short stature, joint misalignments and early OA.
Metaphyseal Chondrodysplasia includes a heterogeneous set of disorders affecting the metaphyses of the long bones and characterized, among other things, by anomalies such as genu varum, coxa vara and short limb dwarfism. The Schmid type, often mistaken for vitamin D deficiency rickets, represents a mild form of it and without intellectual disabilities.
A certain percentage of arthritis is also caused by the pathological deposition of calcium phosphate crystals in the cartilage (fibrous and hyaline), capable of giving rise to chronic pain and inflammation. It is the family of "Calcium PyroPhosphate Deposition Diseases" (CPPD). Chondrocalcinosis is part of this clinical context, although the majority of the forms are not genetically determined and are commonly found in the elderly; type 1, inherited in an autosomal dominant way, is associated with early-onset OA. It has been hypothesized that at the origin of this condition there are cartilage metabolic alterations which increase the concentration of PPi (Inorganic PyroPhosphate) in the synovial fluid.
Type 2 chondrocalcinosis, rare and also with autosomal dominant inheritance, is caused by the deposition of crystals in the vertebral area. The anomaly concerns a protein expressed in joints and other tissues and its consequence, ie the alteration of PPi levels, leads to chondrocalcinosis.
Finally, even the rare metabolic disorder Alkaptonuria can determine the rapid and progressive onset of multiple osteoarthropathies. In this case, it is the accumulation of homogentisic acid (resulting from the metabolism of the amino acids phenylalanine and tyrosine) in the connective tissue and cartilages that causes the classic "ochronotic arthropathy", a degenerative condition that mainly affects the axial and peripheral joints, giving rigidity, pain and increased risk of fractures.
This report analyzes osteoarthritis and the other cartilage syndromes described above.

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