Why are some people misdiagnosed as having Oculocutaneous Albinism when they actually have Hermansky-Pudlak Syndrome?

Patients typically receive a diagnosis of HPS following an unexplained bleeding episode that prompts doctors to investigate further and to test for HPS. The vast majority of people who eventually get a diagnosis of HPS have previously been misdiagnosed as having either a subtype of oculocutaneous or ocular albinism

In the UK, a diagnosis of OCA or OA is typically given by either an ophthalmologist (eye doctor) or a paediatrician (children's doctor).  This is because they are typically the type of doctor that a newborn or child is referred to when albinism is suspected.  HPS is rare and most doctors have never heard of it so when they see a lack of pigment (hypo-pigmentation) and visual impairment they assume that these are symptoms of OCA or OA.

Typically a doctor will make a diagnosis of either OCA or OA based upon level of hypopigmentation and examination of eyes.  This causes problems because both HPS and other forms of albinism share some characteristics.  The tests and criteria used to diagnose OCA and OA focus on those shared characteristics and so cannot be used to reliably differentiate between HPS and the various other subtypes of OCA and OA  These include:

Some doctors make an incorrect assumption the people with HPS have darker pigmentation than people with OCA-1A.  This is true in most cases.  However, some people with HPS have pure white hair and their lack of pigment resembles that of OCA1A.  This has led some doctors to dismiss the possibility of a patient having HPS without offering either a test for HPS or a test to confirm whether they do have OCA-1A.

In fairness most doctors have the very best of intentions for their patients.  It is sometimes the case that patients are not best placed to help doctors come to a correct diagnosis.  For instance:

Tyrosinase status and the hair bulb test

The hair bulb test should NOT be used as a screen for Hermansky-Pudlak Syndrome.

The test has been found to be unreliable and has fallen out of favour.  It may falsely indicate that a patient is tyrosinase negative when in fact they may be tyrosinase positive (explained below).  Such a ‘false negative’ may lead a doctor to prematurely exclude a diagnosis of HPS.

People with HPS are Tyrosinase positive (Tye+).  This means they have an enzyme called Tyrosinase in particular types of skin and hair cells that are involved in the production of the pigment Melanin.  This is also true of people who have the various subtypes of OCA and OA - EXCEPT  those with subtype OCA1A.  People who have OCA-1A are tyrosinase negative (Tye-) and either have no tyrosinase enzyme activity or negligible amounts of the enzyme. They typically have near pure white hair and the retinas of their eyes are very ‘blonde’ (lacking melanin pigment). In fact, even if the hair bulb test were reliable, it would not provide useful information in most cases since nearly all subtypes of OCA (including HPS) are tyrosinase positive conditions.

The hair bulb test involves plucking hair shafts with follicles from a patient’s scalp.  The follicles are incubated in a a chemical (either L-dopa or L-Tyrosine).  These chemicals are ‘naturally’ involved in the production of melanin pigment.  It the hair follicles become brown or black then that indicates that the  tyrosinase enzyme is present and the patient is ‘Ty positive’.  If there is no colour change then the patient is ‘Ty negative’.

Historically some doctors have used microscopes to examine hair follicles for the presence of pigment containing Melanosomes and how ‘mature’ the melanosomes are.  Again the various subtypes of HPS can give similar results to the subtypes of OCA and OA.  Again this approach is regarded as unreliable and in some cases it may indicate that a patient is Ty negative when they are actually Ty positive.

Misdiagnosis of HPS as other types of Albinism

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