Hermansky-Pudlak syndrome

Vilasinee Morkjaroenpong, MD, MPH, A. Polito, MD, S. Georas, MD, P. Terry, MD, MA--Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University Hospital, Baltimore, MD

Introduction: Hermansky Pudlak Syndrome (HPS) was first reported in 1959 by Hermansky and Pudlak. HPS consists of triad of oculocutaneous albinism, absence of platelet dense bodies, and lysosomal accumulation of ceroid lipofuscin. This rare autosomal recessive disease has also been associated with progressive interstitial lung disease. Majority of cases has been reported in patients with Puerto-Ricans ancestry with few reported cases in other ethnicity. This is a case report of rapidly progressive HPS in a pregnant African-American woman.

Case Presentation: A 32 years old African-American female presented to the Ob-gyn service at gestation age of 19 weeks with progressive shortness of breath which started 6 months prior to her visit. This progressive dyspnea on exertion has worsened for the past 2 weeks with accompanying nonproductive cough and no other systemic symptoms. She denied recent ill contacts or exposures to TB, and denied recent travel. Her medical history is significant for a diagnosis of oculocutaneous albinism, fixed gaze nystagmus, and strabismus since birth. She has had five full-term deliveries and three prior abortions without complications. She is an active intravenous drug abuser, and uses heroine, crack cocaine, with multiple unsuccessful attempts at detoxification and was incarcerated for 2 months for possession and skipping court. She is also an active cigarette smoker for half a pack a day for approximately 7 years. On admission, she is hypoxic on room air and afebrile. On examination, she was an albino with brown hair and patchy skin pigmentation. Fixed gazed nystagmus was notable on exams. Bilateral crackles and bilateral clubbing were also noted. Her cardiovascular exam was normal, and she has a gravid uterus, and the size was slightly smaller for her gestational age. Her arterial blood gas showed a pH of 7.42, pCO2 of 30, and PaO2 of 59 on room air. Her white blood cell counts were 6,800 with a normal differential, a hematocrit of 31, and a platelet count of 309,000. Her urine toxicology screen was positive for opiates. Her HIV test was negative as was her PPD test. Her chest x-ray revealed bilateral interstitial infiltrates, and her high resolution CT scan revealed extensive fibrosis and honeycombing with some areas of ground glass appearance (Figure 1 and 2). Based on this CT scan findings and physical exam, the differential diagnosis of usual interstitial pneumonitis, Lymphangioleiomyomatosis (LAM), and Hermansky-Pudlak Syndrome was entertained. Her respiratory status deteriorated despite intravenous empiric antibiotics and she underwent open lung biopsy, which showed extensive fibrosis and honeycombing. She remained, hypoxic requiring mechanical ventilation, with. high level of PEEP and FIO2. She died approximately a month after aggressive therapy with intravenous high doses of steroids and full mechanical ventilatory support. Given her albinism and extensive fibrosis found on lung biopsy (Figure 3), a diagnosis of Hermansky-Pudlak Syndrome was suspected. Blood sample was sent to Dr. James White's laboratory in University of Minnesota, who kindly perform the test and found that this patient's platelet has an absence of dense granules on electron microscopy, which is diagnostic of this disease. After the diagnosis was made, we have re-reviewed the pathology slides and Stand no evidence of ceroid deposition in the lung tissues. On further review of this patient's family tree, there was no linkage to any Puerto-Rican ancestry, but was significant for albinism in several of paternal cousins. Her mother and immediate siblings were not albinos.

Discussion: This patient presented in the terminal phase of interstitial lung disease, which appeared to have progressed rapidly. In Hermansky-Pudlak Syndrome, pulmonary disease begins with a restrictive component and progresses inexorably to death, usually in the fourth or fifth decade of life. It appears that this patient has a very rapid and fulminant course of the disease, but it maybe due to her substance abuse history and lack of medical care, that her pulmonary problems have not come to medical attention before. Pulmonary disease appears to be twice as common in women, occurring between the third and fourth decades. Most of the patients died of diffuse fibrotic lung disease, which resembles idiopathic pulmonary fibrosis. Currently, there is no effective therapy for this diffuse fibrotic process. The NIH is currently enrolling patients with Hermansky-Pudlak syndrome for antifibrotic drug therapy with perfenidone.

Conclusion: Oculoeutaneous albino patients who present with interstitial lung diseases should be tested for this rare disease. Diagnostic tests would include absence of dense granules on electron microscopy of platelets, or a documentation of ceroid lipofuscin deposition in pulmonary macrophages or other organs. This disease, although rare in non-Puerto Rican populations, can occur in almost any ethnicity.

COPYRIGHT 2000 American College of Chest Physicians
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