Original article
Intestinal Disease in Hermansky-Pudlak Syndrome: Occurrence of Colitis and Relation to Genotype

https://doi.org/10.1016/S1542-3565(05)00858-XGet rights and content

Background & Aims: Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction, results from mutations in 1 of at least 7 different genes. Some patients develop a fatal pulmonary fibrosis and others a disabling colitis. This study aimed to document the occurrence of colitis among HPS patients, characterize gastrointestinal tract involvement in HPS, and analyze the distribution of colitis among HPS genotypes. Methods: Of the 122 HPS patients followed at the National Institutes of Health Clinical Center between 1993 and 2005, 24 were evaluated by endoscopy for gastrointestinal complaints. The histology of gastrointestinal biopsies was retrospectively examined to assess for inflammatory changes, granulomata, and pigmented macrophages. These data were compared with symptoms and HPS genetic subtypes. Results: At colonoscopy, 7 of 23 patients (30%) had endoscopic mucosal abnormalities, including nodularity, erythema, petechiae, or erosions. Six of these 7 patients (86%) had findings of colitis on biopsy. Of the 16 patients with normal-appearing colonic mucosa, 2 patients (12%) had colitis on biopsy. Pigmented macrophages were also observed in the colonic lamina propria in 16 of the 23 patients (70%). Of the 8 patients with confirmed colitis, 7 had the HPS-1 subtype, and 1 had the HPS-4 subtype. Conclusions: There is an increased frequency of colitis in our population of 122 HPS patients (8/122, 7%) and in HPS patients referred specifically for symptom evaluation (8/24, 33%). Colitis was found in patients with HPS-1 and HPS-4 genotypes.

Section snippets

Patients

One hundred twenty-two patients with HPS were admitted to the NIH Clinical Center between September 1993 and March 2005. All patients were enrolled in a protocol approved by the Institutional Review Boards of the National Institute of Child Health and Human Development and the National Human Genome Research Institute to study the clinical and molecular aspects of HPS. Written informed consent was obtained from each patient or parent for the purpose of collecting genetic, medical, and clinically

Patient Demographics

The medical records of 122 patients admitted for HPS evaluation were reviewed for endoscopic procedures on the gut. The diagnosis of HPS was established by clinical findings and electron microscopy of platelets (Figure 1). The HPS-1 subtype was most common, occurring in 65% of this group (Table 1). For 10 of the 122 patients, a specific genetic HPS subtype could not be identified; these patients were categorized as “HPS-Type Unknown.”

Twenty-four patients were identified as having had an

Discussion

Our retrospective study of a population of patients with HPS showed that when gastrointestinal symptoms (especially diarrhea and lower gastrointestinal bleeding) were investigated by endoscopy, a high frequency of IBD (8 of 24 patients) could be documented. This IBD can be characterized as primarily colitis, although coexisting terminal ileal inflammation was also noted in the absence of small bowel endoscopic abnormalities (routine examination of the small bowel by imaging studies was not

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    Supported by the Intramural Research Program of the NIH, National Human Genome Research Institute, National Institute of Allergy and Infectious Disease, and the National Cancer Institute.

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