Muller Journal of Medical Sciences and Research

CASE REPORT
Year
: 2014  |  Volume : 5  |  Issue : 1  |  Page : 74--76

Hermansky-Pudlak syndrome


Prabodh Panchadhyayee, Arnab Saha, Kaushik Saha, Rupam Kumar Ta, Pratik Barma 
 Department of Pulmonary Medicine, Burdwan Medical College, Burdwan, West Bengal, India

Correspondence Address:
Kaushik Saha
Rabindra Pally, 1st Lane, P.O. Nimta, Kolkata - 700 049, West Bengal
India

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis and lysosomal deposition of ceroid lipofuscin pigment. Interstitial lung disease may also accompany with the disease. Cases are mainly found among individuals with Puerto Rican ancestry. It develops due to defects in the biogenesis and/or function of lysosome-related organelles essential to membrane and protein trafficking. A 30-year-old Hindu male patient with oculocutaneous albinism, strabismus, nystagmus and severe dimness of vision presented to us for severe shortness of breath. Subsequent investigations revealed he had HPS with an advanced stage of pulmonary fibrosis.



How to cite this article:
Panchadhyayee P, Saha A, Saha K, Ta RK, Barma P. Hermansky-Pudlak syndrome.Muller J Med Sci Res 2014;5:74-76


How to cite this URL:
Panchadhyayee P, Saha A, Saha K, Ta RK, Barma P. Hermansky-Pudlak syndrome. Muller J Med Sci Res [serial online] 2014 [cited 2021 Dec 2 ];5:74-76
Available from: https://www.mjmsr.net/text.asp?2014/5/1/74/128956


Full Text

 Introduction



Hermansky-Pudlak syndrome (HPS) is a very uncommon heterogeneously inherited autosomal recessive disorder which is mainly characterized by a triad of oculocutaneous albinism, hemorrhagic diathesis and pulmonary fibrosis. The syndrome was first observed in the year of 1959 by Dr. Hermansky and Pudlak. [1] There are presence of eight different subtypes of HPS (HPS1-HPS8) on the basis of inheritance of one of the eight known HPS genes. [2],[3] Among all the subtypes of HPS pulmonary involvement is maximum in case of HPS1 and HPS4. [2],[3]

 Case Report



The present case is about a 30-year-old albino man came to our pulmonary medicine outdoor with non-productive cough for last 7 months and persistent progressive dyspnea of modified medical research council grade 4 since 6 months. On further enquiry, he gave a history of occasional epistaxis and gum bleeding since 1 month. He was non-smoker and there was no occupational exposure to known organic or inorganic agents. He denied any history of taking illicit drug use. There was no history of consanguineous marriage in his family and no other relevant family history.

On examination, he had photophobia, divergent strabismus, nystagmus and hypopigmented skin and hair; suggestive of oculocutaneous albinism [Figure 1]a and b. He also had tachycardia and tachypnea with grade 3 digital clubbing. On auscultation of chest there was presence of bilateral basal fine end inspiratory velcro-like crackles. Other systemic examinations were normal.{Figure 1}

Complete blood count was normal. The prothrombin time, partial-thromboplastin time and international normalized ratio was also normal, but there was presence of prolonged bleeding time (16 min; normal: 2-9 min). Chest X-ray showed bilateral reticular opacities in lower and mid zones. On pulmonary function testing, he had restrictive type of ventilatory defect with forced vital capacity (FVC) 43% of predicted, forced expiratory volume in 1 s (FEV 1 ) 48% of predicted and FEV 1 /FVC ratio 96%. High resolution computed tomography (HRCT) scan of thorax revealed bilateral basal predominant reticulations, interlobular thickening, patchy areas of ground glass opacities and subpleural honeycombing suggestive of usual interstitial pneumonia [Figure 2]. We suspected that the patient may have HPS as there was presence of oculocutaneous albinism, hemorrhagic diathesis and pulmonary fibrosis. To confirm the diagnosis bone marrow aspiration was done and it showed megakaryocytes full of dense granules and lipofuscin bodies. The diagnosis was confirmed by platelet electron microscopy which revealed absence of dense bodies in platelets.{Figure 2}

This course of disease was complicated by hospital acquired pneumonia due to pseudomonas infection which was treated by piperacillin-tazobactam with amikacin. However unfortunately though the infection was controlled, the shortness of breath was worsened. Then, he was put on oral corticosteroids at a dose of 1 mg/kg body weight per day along with continuous oxygen therapy. There was no improvement of his symptoms. We then tapered down the dose of corticosteroid and ultimately stopped. The condition of our patient was gradually deteriorated and finally he had passed away.

 Discussion



HPS usually occurs due to unusual formation and transportation of intracellular vesicles in melanosomes, platelets and lysosomes results in the accumulation of ceroid (lipofuscin) bodies. [4],[5] The accumulation of these ceroid bodies within type 2 pneumocytes along with the gathering of surfactant and other molecules in macrophages is the main pathogenesis for the development of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis in HPS appears to be associated with deficiency of surfactant secretion, which leads to the accumulation of giant lamellar bodies in type 2 pneumocytes. [6] This unusual accumulation of proteins in the endosomal compartment results in the aberrant repair and fibrosis in reaction to an injury. [7],[8]

It is very exciting to watch that the proposed hypotheses on the pathogenesis of familial pulmonary fibrosis is almost similar to the above described pathogenesis in which it is shown that due to protein misfolding some proteins like surfactant protein C usually do not function accurately. [9],[10] This leads to trauma to the endoplasmic reticulum, which results in unusual repair response and fibrosis.

The systemic manifestations of HPS are due to the accumulation of a ceroid-like substance in tissue lysosomes. Ceroid is nothing but some wax-like substance. Reticuloendothelial cells, bone marrow and lung macrophages are the main sites for this lysosomal defect. [11] This storage abnormality clinically manifests by restrictive lung disease, granulomatous colitis, renal failure and cardiomyopathy. [12],[13]

The various clinical features of HPS are hematological involvement with easy bruisability, abnormality in the platelet aggregation, interstitial pneumonias mainly pulmonary fibrosis as lung involvement and granulomatous inflammation of the colon as gastrointestinal involvement. The ocular manifestations are refractory errors, astigmatism, pale optic nerves, iris transillumination, congenital nystagmus and photophobia and the dermatological manifestations constitutes of albinism, premalignant and malignant skin lesions. Parental consanguinity is a risk factor of HPS.

Complete hematological evaluation including platelet studies to search for the aggregation of platelets and platelet electron microscopy to observe the absence of dense bodies. [14] The chest radiograph and HRCT of the thorax will reveal the characteristic features suggestive of interstitial pneumonia. Restrictive defect is the predominant abnormality in the pulmonary function test which is also associated with decreased diffusion cavity. [14] The mortality rate of HPS is extremely high. In more than 50% cases of mortality is mainly because of pulmonary fibrosis, 15% cases of mortality is due to hemorrhagic manifestations and 15% cases of death is because of granulomatous colitis.

No definitive treatment except symptomatic is available for HPS. Oral steroids and oxygen supplementation is the mainstay treatment modality of pulmonary fibrosis. Bleeding diathesis is treated with intravenous infusion of desmopressin (0.3 mcg/kg diluted in sterile physiological saline) over 15-30 min. [14]

References

1Hermansky F, Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: Report of two cases with histochemical studies. Blood 1959;14:162-9.
2Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, Izquierdo NJ, Del Fierro L, Muñoz D, et al. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico. J Invest Dermatol 2006;126:85-90.
3Wei ML. Hermansky-Pudlak syndrome: A disease of protein trafficking and organelle function. Pigment Cell Res 2006;19: 19-42.
4Richmond B, Huizing M, Knapp J, Koshoffer A, Zhao Y, Gahl WA, et al. Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking. J Invest Dermatol 2005;124:420-7.
5Huizing M, Gahl WA. Disorders of vesicles of lysosomal lineage: The Hermansky-Pudlak syndromes. Curr Mol Med 2002;2:451-67.
6Guttentag SH, Akhtar A, Tao JQ, Atochina E, Rusiniak ME, Swank RT, et al. Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome. Am J Respir Cell Mol Biol 2005;33:14-21.
7Nakatani Y, Nakamura N, Sano J, Inayama Y, Kawano N, Yamanaka S, et al. Interstitial pneumonia in Hermansky-Pudlak syndrome: Significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes. Virchows Arch 2000;437:304-13.
8Tang X, Yamanaka S, Miyagi Y, Nagashima Y, Nakatani Y. Lung pathology of pale ear mouse (model of Hermansky-Pudlak syndrome 1) and beige mouse (model of Chediak-Higashi syndrome): Severity of giant lamellar body degeneration of type II pneumocytes correlates with interstitial inflammation. Pathol Int 2005;55:137-43.
9Thomas AQ, Lane K, Phillips J 3 rd , Prince M, Markin C, Speer M, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002;165:1322-8.
10Whitsett JA. Genetic basis of familial interstitial lung disease: Misfolding or function of surfactant protein C? Am J Respir Crit Care Med 2002;165:1201-2.
11Di Pietro SM, Falcón-Pérez JM, Tenza D, Setty SR, Marks MS, Raposo G, et al. BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol Biol Cell 2006;17:4027-38.
12Jung J, Bohn G, Allroth A, Boztug K, Brandes G, Sandrock I, et al. Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. Blood 2006;108:362-9.
13Hazzan D, Seward S, Stock H, Zisman S, Gabriel K, Harpaz N, et al. Crohn's-like colitis, enterocolitis and perianal disease in Hermansky-Pudlak syndrome. Colorectal Dis 2006;8:539-43.
14Sen T, Mullerpattan J, Agarwal D, Naphde D, Deshpande R, Mahashur AA. Hermansky-Pudlak syndrome. J Assoc Physicians India 2009;57:660-2.