The NGF gene provides instructions for making a protein called nerve growth factor beta (NGFβ) that is important in the development and survival of nerve cells (neurons), including sensory neurons. The NGFβ protein functions by attaching (binding) to its receptors, which are found on the surface of neurons. Binding of the NGFβ protein to its receptor transmits signals to the cell to grow and to mature and take on specialized functions (differentiate). This binding also blocks signals in the cell that initiate the process of self-destruction (apoptosis). Additionally, NGFβ signaling plays a role in pain sensation. Mutation of the NGF gene leads to the production of a protein that cannot bind to the receptor and does not transmit signals properly. Without the proper signaling, sensory neurons die and pain sensation is altered, resulting in the inability of people with HSAN5 to feel pain. Type 6 -
Hereditary sensory and autonomic neuropathy type 6 (HSAN6) is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection.Genes related to Hereditary sensory and autonomic neuropathy Type 6:
Mutations in the DST (Dystosin) gene are associated HSAN6. In two separate studies of families with presentations of HSAN6, the DST gene was found to be mutated, in one case with a truncating mutation, and in the other a non-sense or missense mutation.
Idiopathic pulmonary haemosiderosis (IPH) is a lung disease of unknown cause that is characterized by alveolar capillary bleeding and accumulation of haemosiderin in the lungs. It is rare, with an incidence between 0.24 and 1.23 cases per million people. Pathophysiology
Being idiopathic, IPH by definition has an unknown cause. It is thought to be an immune-mediated disease. The lung bleeding causes accumulation of iron, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cells which carry oxygen to body tissues for cellular respiration.Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder. PH1 involves PH with circulating anti-GBM antibodies. PH2 involves PH with immune complex disease such as systemic lupus erythematosus, SLE. PH3 involves no demonstrable immune system involvement.A distinct subset of patients with pulmonary hemosiderosis has hypersensitivity to cows milk which result in formation of IgG antibodies against basement membrane. This is called Heiner syndrome. Mechanism of haemorrhage is similar to that observed in Goodpasture syndrome. Related or similar conditions
There are many pulmonary problems that may seem to mimic haemosiderosis but do not necessarily include the deposits of iron into the lung. The deposition of iron in the lungs, occurring in the form of haemosiderin, is the defining characteristic of this illness. These other conditions may occur separately or together with haemosiderosis.