The Hermansky - Pudlak syndrome (HPS ) is a rare inherited disorder in which there is deposition of ceroid in lysosomes, the melanocytes and the Serotoningranula ( δ - granules ) of platelets. The disease is characterized by albinism of the skin and conjunctiva, by an increased bleeding tendency due to a failure of platelet aggregation as well as by the occurrence of pulmonary fibrosis ( interstitial lung disease).
The disease was first described by F. Hermansky and P. Pudlak in 1959 and named after these first authors.
- 4.1 Notes and references
It is the Hermansky - Pudlak syndrome is a very rare disease. Therefore, there is a lack of epidemiological data overall. The disease occurs worldwide sporadically. A geographical clustering of unknown origin there is in the northwest of Puerto Rico. Here (prevalence 1:1800 ) has been reported about 400 sufferers. Exact figures for the German-speaking area are not known.
Etiology and pathogenesis
There are some related with lysosomes membrane-bound vesicles that have the initial stages of their development together. They include the following organelles:
- Serotoningranula, δ - granules or dense granules of platelets
- Azurophilic granules in neutrophils
- Cytotoxic granules in cytotoxic T lymphocytes and NK - cells ( natural killer cells)
- "lamellar bodies" in the alveolar cells or type II pneumocytes
Both the core symptoms as well as less common symptoms that may occur in connection with the Hermansky - Pudlak syndrome, are due to malfunction of these related to the lysosomal vesicles. Albinism is based on a non-working synthesis of melanin in the melanosomes. The bleeding tendency caused by the fact that the platelets in bleeding not clump together ( platelet aggregation ), a process in which the Serotoningranula play a role. Pulmonary fibrosis is due to abnormal "lamellar bodies" in the alveolar cells. In some mouse models of the Hermansky - Pudlak syndrome, are eliminated by the lysosomes. Cytotoxic granules by defective impaired activity of cytotoxic T lymphocytes is induced. A mild Batten disease is probably due to a deteriorated degradation in the lysosomes.
BLOC is an abbreviation for " biogenesis of lysosome -related organelles complex". Literally, this phrase means " to build up complex organelles that are related to lysosomes ."
BLOC1 consists of the HPS7 resin - protein dysbindin, the HPS8 protein Pallidin, Muted, cappuccino, snap, BLOS1 and BLOS2. There may be another previously unknown subunits. Mutations of the dysbindin gene and HPS8 recognized as causing Hermansky - Pudlak syndrome of humans and mice. Mutations of the genes for Pallidin, muted and cappuccino are detected only in mice causes of the syndrome. BLOC1 is needed for the development of specialized organelles that belong to the endosomal - lysosomal system.
BLOC2 consists of HPS3, HPS5 and HPS6. It assigns one of the money for the melanosomes proteins in the early endosomes, the right to transport vesicles or plays a role in the fusion of these transport vesicles with the maturing melanosomes. If BLOC- 2 is not functional, these proteins are not transported to the melanosomes. Stattedessen they move between endosomes and the cell membrane back and forth and eventually dismantled.
To BLOC3 include HPS1 and HPS4. From BLOC4 and BLOC5 is only HPS1 known as an ingredient. BLOC3, BLOC4 and BLOC5 can be found in the cytoplasm and contribute to the formation of organelles such as melanosomes, lysosomes and the Serotoningranula ( δ - granules ) in.
Adapter protein -3 ( AP3 )
The adapter protein 3 ( AP3 ) is distributed in the cytoplasm and transported proteins from the trans - Golgi network and the endosomal network to organelles that are related to lysosomes.
Overview of the various forms of Hermansky - Pudlak syndrome
There are currently no causal therapy. Glucocorticoids have, according to previous study location does not affect the course of disease. The Hermansky - Pudlak syndrome can therefore only be treated symptomatically. The course of the disease, and in particular the progression of pulmonary fibrosis can be obtained by the influence of pulmonary risk factors, such as be adversely affected by smoking. The likelihood of complications, such as the occurrence of a lung inflammation can be reduced by prophylactic vaccination. This primarily includes the pneumococcal and influenza vaccination ( flu shot ). Due to the limited platelet function provide antiplatelet a relative contraindication dar.