1/19. Cutaneous malignancy in albinism.albinism is a disorder of hypopigmentation affecting the skin, appendages, and eyes. Ultraviolet light-induced cutaneous tumors are common in patients with albinism due to reduced or absent protection from melanin. Squamous cell carcinoma (SCC) is the number one skin tumor seen in patients who are albinos. Although nonmelanomatous skin cancers are more common in patients with albinism, dysplastic nevus and melanoma present a greater diagnostic challenge in this group because of their hypopigmented appearance. We report 2 cases of cutaneous malignancies in patients who had oculocutaneous albinism (OCA). The first case involves a 45-year-old man with OCA type 2 (OCA2) who developed a large SCC of the neck. The second case involves a 24-year-old man with Hermansky-Pudiak syndrome (HPS) who developed amelanotic melanoma. In both cases, hypopigmentation of the lesions contributed to a delay in diagnosis. We review the clinical, diagnostic, and therapeutic concerns for patients with albinism who have cutaneous malignancies.- - - - - - - - - - ranking = 1keywords = albinism (Clic here for more details about this article) |
2/19. Hermansky-Pudlak syndrome.A 55-year-old man had oculocutaneous albinism and a history of frequent bruising following minimal trauma. The simultaneous occurrence of these features was first described by Hermansky and Pudlak in 1959. The Hermansky-Pudlak syndrome follows an autosomal recessive trait and is most frequently found in puerto rico and in the Swiss alps. It consists of the triad phenotype of hypopigmentation, prolonged bleeding time due to platelet storage pool deficiency and accumulation of ceroid pigment in lysosomal organelles. Other serious features are pulmonary fibrosis and granulomatous colitis. The disorder is caused by mutations in the HPS1 gene on chromosome 10q23. The HPS1 gene product is involved in the trafficking of melanosomes, platelet dense bodies, and lysosomes.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
3/19. dna diagnosis and management of Hermansky-Pudlak syndrome in pregnancy.Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), platelet storage pool deficiency, and ceroid lipofuscin deposition. Sequelae including pulmonary fibrosis, colitis, and hemorrhagic diathesis can impact obstetric management. An 18-year-old primigravida with OCA was diagnosed during pregnancy with Hermansky-Pudlak syndrome by dna analysis. Uneventful vaginal delivery occurred at term following prophylactic platelet transfusion. women of northwestern Puerto Rican descent with OCA should be offered testing for HPS. Identification of affected individuals may permit optimal obstetric management.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
4/19. Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disease consisting of oculocutaneous albinism and a storage pool deficiency resulting from absent platelet dense bodies. The disorder is genetically heterogeneous. The majority of patients, including members of a large genetic isolate in northwest puerto rico, have mutations in HPS1. Another gene, ADTB3A, was shown to cause HPS-2 in two brothers having compound heterozygous mutations that allowed for residual production of the gene product, the beta3A subunit of adaptor complex-3 (AP-3). This heterotetrameric complex serves as a coat protein-mediating formation of intracellular vesicles, e.g. the melanosome and platelet dense body, from membranes of the trans-golgi network. We determined the genomic organization of the human ADTB3A gene, with intron/exon boundaries, and describe a third patient with beta3A deficiency. This 5-y-old boy has two nonsense mutations, C1578T (R-->X) and G2028T (E-->X), which produce no ADTB3A mRNA and no beta3A protein. The associated mu3 subunit of AP-3 is also entirely absent. In fibroblasts, the cell biologic concomitant of this deficiency is robust and aberrant trafficking through the plasma membrane of LAMP-3, an integral lysosomal membrane protein normally carried directly to the lysosome. The clinical concomitant is a severe, G-CSF-responsive neutropenia in addition to oculocutaneous albinism and platelet storage pool deficiency. Our findings expand the molecular, cellular, and clinical spectrum of HPS-2 and call for an increased index of suspicion for this diagnosis among patients with features of albinism, bleeding, and neutropenia.- - - - - - - - - - ranking = 0.375keywords = albinism (Clic here for more details about this article) |
5/19. Successful thyroidectomy in a patient with Hermansky-Pudlak syndrome treated with recombinant activated factor vii and platelet concentrates.Hermansky-Pudlak syndrome is a rare autosomal recessive disorder characterized by the absence of platelet dense bodies in association with albinism. We present the use of recombinant activated factor vii (rFVIIa) in a patient with Hermansky-Pudlak syndrome who underwent total thyroidectomy because of a large richly vascularized nodule (10 cm) compressing the trachea. The patient had a prolonged bleeding time (> 20 min) that remained unchanged after platelet transfusions. However, after infusion of platelets plus rFVIIa, it diminished to 5 min. The platelet aggregation response to adenosine diphosphate and collagen was diminished. Since an early age, the patient had repeated nose bleeding and an episode of melena requiring several tampons, cauterization and transfusions of packed red cells. In this case, we used rFVIIa in bolus for 1 day (four doses of 120 microg/kg every 2 h and six doses of 100 microg/kg every 3 h) and transfusion of platelet concentrates beginning just prior to surgery. No evidence of local bleeding complication could be detected during the entire post-operative period. The hemoglobin level remained normal and no transfusions of packed red cells were necessary. No adverse events occurred.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
6/19. Variable response of Hermansky-Pudlak syndrome to prophylactic administration of 1-desamino 8D-arginine in subsequent pregnancies.Hermansky-Pudlak syndrome is characterised by oculocutaneous albinism and haemorrhagic diathesis. The bleeding tendency that is associated with this autosomal recessive disease is caused by storage-pool deficiency and has been reported to be controllable by prophylactic administration of 1-desamino 8D-arginine (desmopressin, DDAVP). The DDAVP prophylaxis at the first delivery of our patient did not prevent the severe haemorrhagic sequeal requiring transfusion of packed red cells and platelets, but the same preventive measure was successful at her second childbirth. Response to prophylactic DDAVP administration varies between as well as within patients with Hermansky-Pudlak syndrome.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
7/19. Hermansky-Pudlak syndrome type 1: gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases.Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder causing oculocutaneous albinism and a platelet storage pool deficiency, reflecting defective biosynthesis and/or processing of melanosomes and platelet dense bodies. Four human genes (HPS1, ADTB3A, HPS3, HPS4) are associated with four subtypes of HPS. The most common is HPS-1. A 16-bp duplication in exon 15 of the HPS1 gene causes HPS-1 in 450 northwest Puerto Rican patients; 13 other HPS1 mutations have been reported in non-Puerto Rican patients. We screened 26 HPS patients, who lacked a molecular diagnosis, for HPS1 defects and identified six patients with six different HPS1 mutations. Four novel mutations were discovered, including the first HPS1 missense mutation, 922T>C, in exon 8. This mutation, along with 624delG in exon 6, preserve rna transcription, while 561delC in exon 5 and [1581delA;1594C>A] in exon 14 produce no rna on northern blot. One of six adult patients developed pulmonary fibrosis, and two patients ages 16 and 17 have granulomatous colitis. These complications are common among Puerto Rican HPS-1 patients but have not appeared in HPS-2 or HPS-3 patients. The diagnosis of HPS-1, available only on molecular grounds, has important prognostic and treatment implications.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
8/19. A clinical variant of familial Hermansky-Pudlak syndrome.Hermansky-Pudlak syndrome (HPS) is an autosomal recessive inherited disease consisting of (1) partial oculocutaneous albinism (with nystagmus, strabism, and visual acuity loss), (2) platelet storage pool deficiency (with bleeding diathesis), and (3) disorder of "ceroid" metabolism with a multisystem tissue lysosomal ceroid deposition. HPS is less uncommon in puerto rico, where the most important studies have been performed, but is a very rare disease in europe. HPS basic defect remains unknown, even if an HPS-causing gene was identified in chromosome segment 10q23-q23.3, and several mutations have been reported. The aim of this article is to discuss, on the basis of a review of relevant literature, a new familial HPS clinical variant observed in 2 young sisters (aged 16 and 23 years old, respectively), characterized by the typical symptoms of this syndrome. Our patients also suffered from diffuse interstitial pulmonary disease and an unexpectedly increased platelet aggregation and were prone to bacterial infections. Interestingly, we observed urinary tract abnormality in the younger HPS sister and a porencephalic cyst in the older HPS sister; both of these developmental defects have been reported in the Cross syndrome (or oculocerebral hypopigmentation syndrome). It seems that in our patients, an overlapping of the phenotypic manifestations of different rare syndromes may be present. The presence of ceroid-like autofluorescent material in urinary sediment together with the histologic aspects and the autofluorescence of oral mucosa biopsy are consistent with a ceroid-like lipofuscin storage. HPS should be carefully tested for in suspected cases to prevent the severe visual impairment, rapidly progressive pulmonary fibrosis, and other complications associated with this disorder.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
9/19. Hermansky-Pudlak syndrome type 4 in a patient from sri lanka with pulmonary fibrosis.Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency. Some patients also develop fatal pulmonary fibrosis and some have granulomatous colitis. Six human genes HPS1, ADB3A, HPS3, HPS4, HPS5, and HPS6 have been identified as cause of the six known subtypes of HPS. While there exist nearly 500 Puerto Rican and non-Puerto Rican HPS-1 patients, very few HPS-4 patients have been reported, and most of these have not been described in detail. We now delineate the clinical characteristics of an HPS-4 patient homozygous for a novel HPS-4 mutation, P685delC. The patient, the first individual with HPS reported from sri lanka, had severe pulmonary fibrosis, typical of HPS-1 disease, without granulomatous colitis. We conclude that pulmonary fibrosis occurs as part of HPS-4 and that HPS should be considered in all ethnic groups.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
10/19. Hermansky-Pudlak syndrome in a pregnant patient.Hermansky-Pudlak syndrome is a multisystem disorder with albinism, bleeding diathesis and visual impairment as the main features. We report a case of epidural analgesia in a pregnant patient, who was subsequently discovered to have this syndrome. We believe this to be the first such report.- - - - - - - - - - ranking = 0.125keywords = albinism (Clic here for more details about this article) |
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