Two Complex Cases of Hermansky-Pudlak Syndrome Highlight a Potential Biologic Explanation for an Associated Crohn's Disease Phenotype

Sofia, M. Anthony; Sakuraba, Atsushi; Rubin, David T.

doi:10.14309/crj.2017.14

Cited by 8 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Granulomatous colitis was described as a complication of HPS for the first time in 1980[8]. Since then, many cases of inflammatory bowel disorders have been described, including those of colitis, enterocolitis or perianal disease[3,4,9-12]. These gastrointestinal complications are associated with HPS 1 and HPS 4 subtypes, occur in 20%-30% of the cases[3,4], and have been the cause of death in 9% of the deceased HPS patients in Puerto Rico[6].…”

Section: Discussionmentioning

confidence: 99%

“…The granulomatous colitis associated with HPS shares features with both ulcerative colitis and CD. In fact, clinical presentation and friable erythematous mucosa with ulcerations from rectum to cecum are suggestive of ulcerative colitis[10-12], but they present pathologic findings consistent with CD and can be associated with perianal and perirectal disease resembling the typical anorectal findings often seen in patients with CD[4,9,12].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Crohn’s-like acute severe colitis associated with Hermansky-Pudlak syndrome: A case report

Girot¹,

Berre²,

Maissin³

et al. 2019

WJG

View full text Add to dashboard Cite

BACKGROUND Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage pool deficiency and systemic complications associated with ceroid deposition in the reticuloendothelial system. HPS types 1 and 4 are associated with Crohn’s disease (CD)-like gastrointestinal disorders, such as granulomatous enterocolitis or perianal disease. Cases of colitis can be particularly severe and, before the use of anti-tumor necrosis factor alpha (TNFα) therapy had become common, were reported as showing poor responsiveness to medical treatment. CASE SUMMARY We present the case of a 51-year-old albino woman who presented with acute severe colitis that led to the diagnosis of HPS. Histologic findings of biopsy samples showed chronic inflammation with deep ulcerations, and granulomas without caseous necrosis. Molecular genetic analysis confirmed HPS type 1, with a homozygous 27 base-pair deletion in exon 20 of the HPS1 gene. Once the patient’s bleeding diathesis was corrected by platelet transfusion, the granulomatous colitis responded dramatically to a medical treatment regimen that included corticosteroids, azathioprine and infliximab; this regimen is similar to that used in CD treatment. Although it remains unclear if the granulomatous enterocolitis in HPS is due to ceroid deposition or reflects the co-existence of CD and HPS, the fact that this case of HPS-related granulomatous colitis responded to the same therapeutic approach used in CD suggests that this type of colitis may result from HPS patients’ genetic susceptibility to CD. CONCLUSION We report a case of severe colitis that led to the diagnosis of HPS, which was responsive to azathioprine and infliximab.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Crohn’s-like acute severe colitis associated with Hermansky-Pudlak syndrome: A case report

Girot¹,

Berre²,

Maissin³

et al. 2019

WJG

View full text Add to dashboard Cite

show abstract

“…The colitis may respond to corticosteroids or anti‐TNF‐α drugs; surgical bowel resection is performed in refractory cases (Demirtas, Alahdab, Kani, Atug, & Imeryuz, 2019; Kouklakis et al, 2007; Mora & Wolfsohn, 2011). Abnormal endosomal membrane formation was suggested as an underlying cause for HPS colitis leading to ceroid lipofuscin formation, abnormal autophagy and phagocytosis, and inflammation (Felipez et al, 2010; Sofia et al, 2017). It was suggested that the presence of risk alleles in Crohn's disease‐associated genes, like NOD2 or ATG16L1 , in HPS subjects may contribute to developing colitis (Lozynska et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…The underlying cause remains unknown. Abnormal endosomal (LRO‐related) membrane formation was suggested, leading to ceroid lipofuscin formation, abnormal autophagy and phagocytosis, inflammation (Felipez, Gokhale, & Guandalini, 2010; Sofia, Sakuraba, & Rubin, 2017). Some BLOC‐2 or BLOC‐3 deficient cases develop colitis (Huizing et al, 2000; Hussain et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Hermansky–Pudlak syndrome: Mutation update

et al. 2020

View full text Add to dashboard Cite

Hermansky-Pudlak syndrome (HPS) is a group of 10 autosomal recessive multisystem disorders, each defined by the deficiency of a specific gene. HPS-associated genes encode components of four ubiquitously expressed protein complexes: Adaptor protein-3 (AP-3) and biogenesis of lysosome-related organelles complex-1 (BLOC-1) through -3. All individuals with HPS exhibit albinism and a bleeding diathesis; additional features occur depending on the defective protein complex. Pulmonary fibrosis is associated with AP-3 and BLOC-3 deficiency, immunodeficiency with AP-3 defects, and gastrointestinal symptoms are more prevalent and severe in BLOC-3 deficiency. Therefore, identification of the HPS subtype is valuable for prognosis, clinical management, and treatment options. The prevalence of HPS is estimated at 1-9 per 1,000,000. Here we summarize 264 reported and novel variants in 10 HPS genes and estimate that~333 Puerto Rican HPS subjects and~385 with other ethnicities are reported to date. We provide pathogenicity predictions for missense and splice site variants and list variants with high minor allele frequencies. Current cellular and clinical aspects of HPS are also summarized. This review can serve as a manifest for molecular diagnostics and genetic counseling aspects of HPS.

show abstract

“…Twenty percent patients of HPS associated with granulomatous colitis. The HPS types 1 and 4 are associated with a granulomatous enterocolitis affects in first or third decade [26,27]. Upper gastrointestinal involvement is rare with evidence of gastroduodenal ulcer with lymphocytic infiltration [28].…”

Section: Systemic Involvementmentioning

confidence: 99%