Although it is unknown how changes in this enzymes function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a related disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other gene may be involved.Mutations in the NAGA gene, resulting in alpha-N-acetylgalactosaminidase deficiency, cause an infantile neuroaxonal dystrophy known as Schindler disease. Diagnosis
In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly. Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding and breathing problems that can lead to frequent infections, such as pneumonia.
Tumoral calcinosis is a rare condition in which there is calcium deposition in the soft tissue in periarticular location, around joints, outside the joint capsule. They are frequently (0.5–3%) seen in patients undergoing renal dialysis. Clinically also known as hyperphosphatemic familial tumoral calcinosis (HFTC), is often caused by genetic mutations in genes that regulate phosphate physiology in the body (leading to too much phosphate (hyperphosphatemia)). Best described genes that harbour mutations in humans are FGF-23, Klotho (KL), or GALNT3. A zebrafish animal model with reduced GALNT3 expression also showed HFTC-like phenotype, indicating an evolutionary conserved mechanism that is involved in developing tumoral calcinosis. Clinical features
The name indicates calcinosis (calcium deposition) which resembles tumor (like a new growth). They are not true neoplasms – they dont have dividing cells. They are just deposition of inorganic calcium with serum exudate. Children and adolescents (6 to 25 years) are the most commonly affected. The symptom that the accumulations cause is not pain but swelling around joints. They have propensity to enlarge progressively and ulcerate the overlying skin and extrude. They are most common around shoulders, hips and elbows. Laboratory evaluation reveal normal serum calcium levels and hyperphosphatemia. Rarely ALP (alkaline phosphatase – an enzyme active at sites of bone formation) may be elevated. Treatment is normalization of serum phosphate levels and resection of lesions. Surgical removal should be complete and if part of it is left, recurrence is likely to occur. Cutting through the excised calcium deposition reveals semifluid calcium suspension in albumin encapsulated by fibrous tissue.