Title: The Albino Masquerader: Hermansky-Pudlak Syndrome and its Inherent Risks and Systemic Effects Authors: Matthew Roe, OD; Alexandria Tilley, OD; Andrea Thau, OD, FCOVD, FAAO, DPNAP

Abstract: Hermansky-Pudlak Syndrome is a multi-system condition with resulting tyrosinase-positive albinism. This poster seeks to discuss necessary precautions in such patients and why optometrists must rule-out HPS in oculocutaneous albino patients.

I. Case History  Patient Demographics: 4 month old white female of Eastern European descent  Chief Complaint: Parental concern of lack of fixation, tracking, and eye contact, as well as the presence of nystagmus  Ocular/Medical History:  Bilateral foveal hypoplasia  Nystagmus present since birth, which has decreased in speed over time  Currently undergoing genetic testing  Current Medications: none  Other pertinent information: no known family history of albinism

II. Pertinent findings  Clinical:  VAs: 20/710 OU c Teller @ 55cm, questionable fixation  EOMs: full with no restrictions; moderate amplitude, low frequency pendular nystagmus that dampens with convergence  DCT/NCT: ortho  Bruckner: equally bright OU  Pupils: PERRL(-) APD  Damp Mohindra Retinoscopy: +3.00sph OD/OS  Anterior segment: Iris transillumination 360 OD/OS  Physical:  Dilated Fundus Exam: Gray nerves with distinct borders OD/OS; foveal hypoplasia OD/OS, blonde fundus to extent seen OD/OS

III. Differential diagnosis  Hermansky-Pudlak Syndrome 1. Confirmed via genetic testing by 4-month follow-up examination  Tyrosinase-positive Oculocutaneous Albinism  Chediak-Higashi Syndrome  Waardenburg Syndrome

IV. Diagnosis and Discussion  General . Hermansky-Pudlak Syndrome is a rare genetic defect with manifestations in multiple systems inherited in an autosomal recessive pattern. It is found in 1:500,000-1:1,000,000 live births worldwide,1 except in the Puerto Rican population with an increased prevalence of 1:1800.2,3 Patients exhibit tyrosinase-positive ocular albinism, hemorrhagic diathesis secondary to platelet storage pool defects with normal platelet body counts, and ceroid deposits throughout the body. . The syndrome is caused by a mutation to one of the eight HPS genes involved with membrane function and protein trafficking. Patients are often found to bruise easily, have light skin pigmentation that can darken with age, and prolonged bleeding. Patients also develop inflammatory bowel disease with symptoms similar to that of Crohn’s Disease.4 Additional systemic involvement includes renal tubular epithelium and cardiac muscle. . Presentation and history alone may draw suspicion to the diagnosis of Hermansky-Pudlak Syndrome. However, it is important to confirm via genetic testing to rule out other differential diagnoses. Additionally, genetic testing will establish the specific subtype of the syndrome, as certain mutations result in more severe debilitation. Platelet body biomicroscopy may also be performed to further confirm the general diagnosis of HPS. . Life-expectancy may be drastically reduced, depending on the subtype. In the most severe case, patients develop pulmonary fibrosis in their third or fourth decade of life with resultant death usually by the fifth decade.5 . Due to platelet dysfunction, platelet transfusions must be utilized for all surgeries in HPS patients.  Patients with HPS present with nystagmus secondary to foveal hypoplasia, resulting in reduced visual acuities ranging from 20/50-20/200. Other ocular signs include strabismus, albino fundus, and iris trans-illumination.  Case Study  This patient had been diagnosed with Hermansky-Pudlak Syndrome at age 4 months. She has yet to undergo any procedures or surgeries secondary to the diagnosis, and no bruises were noted at the time of examination. Initial visual acuity with Teller cards showed reduced vision of 20/710 which improved without spectacle correction or nystagmus surgery to 20/50 when measured with Cardiff cards after one year. No strabismus was noted in any examination.

V. Treatment and Management  General . Non-invasive procedures for management of nystagmus include: full refractive correction, yoked-prism to utilize null-point, vision therapy to correct any binocular and accommodative dysfunctions, and biofeedback through contact lenses. In the future, low vision devices may be employed to help maximize visual potential. . Nystagmus surgical intervention may be performed after non-invasive procedures have been exhausted. Procedures currently employed include the Kestenbaum-Anderson procedure, four-muscle recession, and four-muscle tenotomy, as well as any combination of the three. Strabismus surgery may be performed concurrently if necessitated.  Case Study  Proper patient education is vital for not only ocular health, but overall health. In terms of ocular health, patients must be provided with adequate UV-protection due to lack of pigmentation. Additionally, large-brimmed hats were recommended for overall ocular adnexa skin protection.  Visual acuities have been found to improve following nystagmus surgery. If referring for nystagmus or strabismus surgery, the surgeon must be made aware of excessive bleeding in order to take the necessary precautions. Platelet transfusion has been shown to significantly decrease bleeding time in HPS patients when undergoing surgical procedures.  The patient was asked to return at three-month intervals for one year in order to monitor improvement in acuity. Visual acuity had stabilized with Cardiff acuity cards after one year with minimal refractive error measured via Mohindra retinoscopy. The measured refractive error at each successive follow-up did not contain amblyogenic factors and was not shown to improve acuity or dampen the patient’s nystagmus. The importance of UV-protection was reinforced, and the patient is now to be monitored on an annual basis.

VI. Conclusion  Optometrists play a vital role in the diagnosis and management of Hermansky-Pudlak Syndrome patients. Oculocutaneous albinism warrants genetic testing, especially in the absence of a positive family history, in order to rule out underlying systemic conditions which may impact patient quality of life.  To reduce nystagmus, it is necessary to consider the following non-invasive procedures: full refractive correction, yoked prism, vision therapy for binocular dysfunctions and accommodative dysfunctions, and biofeedback through contact lenses.  If referring for ocular surgery, it is imperative to include the syndrome’s symptom of prolonged bleeding secondary to platelet body pooling deficiencies. If unaddressed, the patient faces serious risk of extensive bleeding while undergoing the procedure.  Early diagnosis and understanding of Hermansky-Pudlak Syndrome, for both the optometrist and the parents, is vital to maximizing visual potential. Optometrists must ensure that the patient receives proper UV-protection, spectacle prescription, and necessary vision rehabilitation and low-vision devices in the future.

Sources

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