Latest / EHA Unplugged / Hematologists’ Role in the Management of Gaucher Disease (Prof Argiris Symeonidis and Prof Sam Salek)

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Hematologists’ Role in the Management of Gaucher Disease (Prof Argiris Symeonidis and Prof Sam Salek) · EHA Unplugged

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  Gauche disease is a metabolic disorder, is a systematic
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  disease being classified to the so-called lysosomal storage
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  disorders, and actually in this group is considered the most
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  common, although of course is a rare disease, as the whole group
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  of these diseases belong to the category of rare diseases.
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  Welcome to the EHA Unplugged, the official podcast of the
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  European Hematology Association EHA.
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  I'm your host, Professor Sam Selleck, and today's guest is
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  Professor Igress Simonidis. Professor Simonidis is the
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  Professor of hematology in the University of Porteras, Greece,
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  and he's also the president of the Greek MD's study group, and
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  in addition to that is the country coordinator of Greece in
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  the European MD's registry. He also is a founder and the
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  coordinator of the Greek National MD's registry.
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  In terms of his interest, he's AMDSA specialist, bone marrow
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  failure specialist and plasma cell discrases, and most
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  importantly, a specialist in negotiate disease.
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  Professor Samadiyas, welcome to this podcast.
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  There are some thanks for inviting me to this interesting
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  discussion and I think we are going to discuss on a very
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  fascinating disease which is actually rare disease.
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  However, there is a strong involvement of the hematologist
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  and of the area of hematology in the management of this disease.
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  So I think we should show with you our discussion this
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  contribution of our specialty of hematology in order to alert all
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  hematologist that they should be aware of the presence of this
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  disease. Well, thank you for that though,
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  Grace. I'm really looking forward to
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  the conversation that we're going to have about the
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  importance of the curriculum for the hematologist in the field of
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  the negotiate disease and the associated aspect that are
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  related to that curriculum. So let's just start with my
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  first discussion Point Argos, Could you tell us what kind of
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  disease is gauche disease? Yes, well, gauche disease is a
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  metabolic disorder, is a systematic disease being
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  classified to the so-called lysosomal storage disorders.
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  And actually in this group is considered the most common,
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  although of course is a rare disease, as the whole group of
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  these diseases belong to the category of rare diseases.
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  Gauche disease stems from a mutation occurring in the
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  glucose cerebrosidase gene which results in the accumulation of
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  an undigested metabolic compound which has to be transported and
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  accumulated in the organs of the reticulum of failure system thus
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  resulting in the enlargement of the organs of the
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  reticulonothalial system. There are several consequences
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  of this pathophysiology and the this result in the clinical
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  manifestation of the disease. It is a systematic disease
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  affecting many aspects, organs and systems, and one of the main
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  specialties involved is the specialty of hematology.
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  Is Scotia disease a pediatric or an adulthood disease?
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  Yes. Well, the answer to this
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  question depends on the age of clinical manifestation of the
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  disease. In the most severe forms of the
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  disease, the clinical manifestations comes early and
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  so the main doctor dealing with disease might be the
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  paediatrician. For 60% of the cases, the first
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  manifestation of the disease come in adulthood, in second or
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  third decade of life and occasionally even later, so that
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  the affected person, the affected patient is quite
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  unaware of the presence of this disease and maybe referred to a
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  specialist who is not aware about the presence of this
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  disease. So if we are considering a young
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  hematologist who doesn't know very much about the Gaucher
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  disease, what a really the main manifestation, perhaps if you
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  could mention one or two that would make the young
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  hematologist suspicious of a Gaucher disease.
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  I would say that the main manifestation of this disease is
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  are practically the enlargement of the liver and spleen and
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  particularly the spleen. And the severity of this
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  enlargement is directly related to the severity of the mutation
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  producing the disease. That means that in the most
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  severe cases, splenomegaly might be severe and symptomatic,
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  whereas in the less severe cases splenomegaly might be almost
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  asymptomatic. I would like now to focus on the
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  epidemiology of the Gochet disease.
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  How common or rare is it? Yeah.
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  It is really a rare disease. It has been estimated that we
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  have one birth of an affected person on average every 40 to
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  50,000 births. This is incidence in the general
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  population. However, there are some ethnic
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  differences, several ethnic differences, and the the disease
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  is much more common among the asking acid juice in which
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  disease occurs with an incidence of 1 affected person every 850
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  births. That is a a frequency of 50
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  times more common than what is occurred in the general
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  population. Do you mentioned something that
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  obviously sparked another point for me and that is, despite the
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  fact that it's rare, which part of the world you find the
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  majority of the prevalence? Well, I would also like to to to
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  mention the point prevalence in the general population.
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  The point prevalence is considered to be 1 affected
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  person every 100,000 people. But this is the precisely
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  diagnosed cases, and it is estimated that one additional
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  case exists which is as yet an undiscovered.
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  So the real incidence by might be twice as high as that I
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  described. Previously you mentioned that
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  it's more prevalent in Ashkenazi.
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  Yes, of course. So this is 50 times for Co,
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  right? So does that mean that they are
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  more prevalence in places such as Israel?
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  For yes. This is correct.
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  Now in terms of the important aspect of the diagnosis of
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  negotiated disease, which one of the consequences would be
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  related to the delayed diagnosis.
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  So in terms of, you know, for example, when the hematologists
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  get a chance to see the negotiated disease, would that
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  be at the start of the diagnosis or when they find their way to
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  hematologies pretty much in the latest stage?
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  This is is mainly manifested with enlargement of the organs
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  of reticular hemophilion system and particularly the spleen.
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  But if the disease will not be discovered at early stage, the
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  consequence should be that the undigested component will
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  accumulate in other organs in the macrophages and enriched in
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  other organs, in particular the bones.
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  And as a result, these disease in late diagnosis might be,
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  might be associated with bone disease of different severity.
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  And the in some cases this is this severity is high and may
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  mimic neuroplastic disorders associated with bone
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  destruction. So for example, this might
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  really mimic metastatic bone disease or multiple myeloma or
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  in other cases and bone cysts, which might be considered
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  initially as benign. But this then they are enlarged
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  and they are producing symptoms including also abnormal
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  fractures, bone fractures in other cases before the the level
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  of structures of bone structures, the patient
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  experience bone pain which is sanded and let's say of a
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  variable civility. And sometimes it comes with a
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  frequency and with a high intensification and this is
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  called bone crisis. Such bone crisis may manifest in
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  the late, in the later stages of the disease.
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  And this I would say, are the consequences of the late
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  diagnosis. Other consequences of the late
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  diagnosis might be the development of virus unpredicted
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  neurological manifestations which are also unpredictable and
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  may lead the patient to address a neurologist.
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  Particularly, this is more common among the most severe
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  cases and in the so-called type 3 of the disease, and of course,
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  in type 2 and are less prominent in the most common type 1, the
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  less severe type of. You mentioned different types of
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  Gochet disease, which you briefly just describe type 1-2
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  and three. Which one of those are more
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  prone to present itself as a late diagnosis?
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  The most common type is the type one of the disease and this is
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  the less severe type usually diagnosed in late childhood or
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  in the adulthood. Maybe we have experience in
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  diagnosing Type 1 patients who said this is even at the age of
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  40 and 50 year old. So this type of disease is
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  usually less symptomatic and the doctor, the treating physician
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  should evaluate the patient carefully and understand and
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  realize when has to start interfere with the progress of
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  the disease. Beside the type one there are
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  two other forms which are called neuronopathic forms of the
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  disease and the most severe is type 2 and type 2 is the result
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  of severe mutation abrogating completely the function of
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  glucoserebrocidase is and thus is is associated with neurologic
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  manifestation early in life. So these patients should start
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  immediately treatment as as soon as the disease has been
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  diagnosis in the early months even when the appropriate
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  treatment this has administered. This has the most dismal
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  prognosis and the child's may not be develop very well, they
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  may show growth retardation, severe organ involvement and
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  finally they might succumb not reaching the even the 10th year
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  of life. There is 1/3 type, the so-called
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  late neuronopathic type or type 3 disease, which is discovered
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  in childhood but not in the first year of life and this can
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  be diagnosed and demand specific type of treatment and when
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  appropriately treated this patients might have a better
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  prognosis than those of type 2 disease.
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  So far, the conversation has brought me to two important
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  points. From my point of view, do you
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  think that the establishment of a curriculum for hematologists
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  focusing on Gocha disease would somehow help with the early
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  diagnosis of Gershey disease? Yes, but that's my first point.
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  And my second point is that you mentioned the neurological
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  impairment. Would you say that those who
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  havegoshiate disease are more prone to developing things such
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  as Parkinson's disease? Yeah.
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  First, I have to say why and in which circumstances the
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  hematologist is involved in the diagnosis and potentially in the
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  treatment of this disease. As I mentioned, the patients
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  developed or organomegaly resulting in peripheral blood
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  cytopenians and among them the most common common is
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  thrombocytopenia. Therefore, when a patient is
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  discovered having thrombocytopenia is very is
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  usually referred to the hematologist for the
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  identification of the cause of thermocytopenia.
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  Either this might be autoimmune or might be no plastic and the
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  this is one of the main reasons of referring patients who go say
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  this is to the to a hematologist.
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  Other reason is the discovery of the ideology of splenomegaly
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  with a potential suspicion of a lymphoma or over a low grade
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  usually lymphoma and in rare circumstances there are some
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  uncommon not easily classified a more attic manifestation.
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  So bruisiness and bleeding and the OR maybe findings of
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  unexpected hyperphyridinemia. All these are reasons which may
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  guide the referral of patients to a hematologist.
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  On top of that very common manifestation of a serum M
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  component and with a potential diagnosis of monoclonal
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  gammopathy of undetermined significance.
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  This is also a very common cause of referral of referring the
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  patient to a hematologist. If the hematologist will
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  approach the suspicion for the presence of this disease, one
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  might go ahead and perform the appropriate diagnostic test to
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  establish the diagnosis. Otherwise, the hematologist
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  might go directly to perform bone more examination which is
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  not officially indicated for the establishment of diagnosis of
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  this disease. And the unexpectedly find that
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  the more bone marrow is, let's say, infiltrated, or there is an
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  accumulation of abnormal monocytes, macrophages, which
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  has the typical morphology of the so-called Gaucher cells.
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  And thus establish the diagnosis of this disease.
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  I again emphasize that performing bone marrow
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  examination is not necessary and should not be performed.
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  But whenever there is no suspicion of the disease, this
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  is a way in weights with weights, a doctor, a
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  hematologist riches the diagnosis of this disease.
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  Now regarding the contribution of other specialties, of course,
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  as a systematic disease, there are many specialists which
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  contribute to the potential diagnosis and of course to the
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  appropriate treatment of the disease.
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  First of all, I would mention the endocrinologist because one
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  major symptom symptom is growth retardation.
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  I would also mention the orthopedics and the
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  rheumatologist whenever the patient money has manifestation
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  of bone pain and bone disease or arthralzias.
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  And in rare occasion I would mention also the pulmonologists
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  and the cardiologists when in some let's say more severe
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  cases, the patient is referred to such specialties.
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  On top of those, I would also mention the role of the
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  neurologist because as you have many patients develop neurologic
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  manifestation and with particularly high higher than
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  expected incidence of sign of parkinsonisms which is
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  manifested early in life. So I would say that just because
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  there is a path of your path for physiological interrelation and
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  connection with the development of Parkinsonism, whenever this
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  is suspected or diagnosed in as not a late, let's say
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  degenerative disease of the late adulthood.
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  In all other circumstances, the neurologist should be aware for
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  the potential presence of Gaussian disease.
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  That's very helpful. Thank you.
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  Now I want to at this stage focus on patient because after
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  All, in all the activities that is focused on diagnosing and
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  treating Gaussian disease, who is that they receive in that?
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  Now you are the vice chair of the Gosha Disease Task Force for
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  the European Hematology Association.
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  I understand that when you had your meeting yesterday, a young
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  hematologist from Italy approached you and expressed
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  interest that she wants to specialize in particular in
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  Gosha disease. Now with the fact that you have
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  mentioned all these other specialities that feed into
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  treatment and diagnosis of Gosha disease, what would be your
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  advice in terms of that young hematologist who wants to
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  develop interest in Gosha disease, in terms of how to
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  communicate with our specialities that would make it
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  easier and understandable that the patients would be able to?
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  Find its way through this maze of number of specialities.
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  The hematologist has a great and the primary, let's say
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  contribution in the diagnosis and potentially the treatment of
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  these disease. As I mentioned, he or she may
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  receive referrals to evaluate patients with common symptoms
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  found in a dermatological disorder, but also because there
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  are several consequence of the late disease associated with
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  with neoplastic hematological disorder and there there is an
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  association of this disease with multiple myeloma incidents of
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  developing monoclonal gammopathy of undetermined significance.
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  The hematologist should be Capablen should be aware of the
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  presence of this disease, so the hematologist should have the
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  option to spend some small period of his training course in
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  expert centres treating patients with this disease and the.
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  By so doing, I think that every hematologist has to gain many
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  things because after all Gauchet disease is a very fascinating
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  disease from the field. From the aspect of research,
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  there are too many open as yet aspects for research which have
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  not been completely identified regarding the pathophysiology of
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  this disease. I would mention the strong
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  immune component of this disease.
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  I would also mention the association with neuroblastic
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  disorders particularly of B lymphocyte or it's in on top of
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  multi myeloma that is a high incidence and high prevalence of
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  B cell malignancies including various types of lymphoma.
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  In some instances Gosa disease has been diagnosed on top of the
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  initial diagnosis of anoplastic malignancy.
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  I practically has experience on such a patient who was diagnosed
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  with Hodgkin lymphoma and upon performing staging for this
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  lymphoma, suddenly we encountered the presence of
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  gorset cells in the marrow. So then gorset disease was
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  established biochemically and that that was a discovery of a
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  patient with no plastic malignancy with lead after all
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  to the diagnosis of gorset disease.
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  So I think that the hematology should be aware.
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  Well, we're fast approaching the end of our conversation and
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  there are two points that I must raise.
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  First of all, I really want to see in your opinion, what are
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  the current effective treatment for negotiate disease?
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  And secondly, what is the prevalence of premature death in
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  Goshi disease? Well, regarding the type of
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  treatment, we have effective enzyme replacement therapy
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  following the manufacturing of the normal enzyme, which is
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  cerebrosidase and the glucose cerebrosidase.
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  And thus patients have the opportunity to be treated let's
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  say theologically because they are receiving replacement
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  therapy as part as a correction of the malfunctioning enzyme.
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  Beside these, there is another treatment option which directs
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  towards the elimination of the formation of the abnormal
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  substrate and this is usually used in let's say less severe
• 24:22
  cases. By using these two treatment,
• 24:25
  two different treatment modalities, patients have been
• 24:29
  happy that they can at least the less severe cases that the
• 24:34
  patients with type 1 disease may have almost quite normal, let's
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  say life expectancy and only barely affecting their quality
• 24:43
  of life. But this of course is attributed
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  to patients with type 1 disease as I mentioned in the beginning,
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  patients with type 2 disease unfortunately and despite the
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  effective treatment of enzyme replacement therapy or substrate
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  reduction therapy, they develop, they develop severe neurologic
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  manifestation and neurologic degeneration.
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  And that that means that this treatment may not be enough to
• 25:18
  effectively reverse the consequence of the disease.
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  Whereas pensions with type 3 disease have shown a very good,
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  let's say response to combine modality therapy and that has
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  reads to a very important prolongation of his of their
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  life expectancy. Thank you very much indeed,
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  Professor Simmondez, as this has been a very enlightening
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  conversation to have. And I would like to thank you
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  for being with us. And I would like to thank the
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  audience for listening and stay tuned with us for more episode
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  of the Gosha Disease. This has been most educational.
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  Thank you. Also Sam, thank you for giving
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  me the opportunity to have this discussion and creating to this
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  podcast. And as soon as the every
• 26:14
  hematologist will realize how nice is diagnosed and treating
• 26:22
  patient with this disease, he or she is going to be happy learn
• 26:28
  more and being more effective in the management of this disease.
• 26:32
  Thank you very much. Thank you very.
• 26:33
  Much indeed.