ORPHA:616874 + group of disorders

[Orphanet-ES]

Dear all,

As I understand it, according "Why ORPHAcoding" presentation, the orpha ORPHA:616874 (Rare disorder without a determined diagnosis after full investigation) should be used in conjunction with a disorder group ORPHAcode to guide future diagnosis.

But, if the disease has a multisystemic presentation, how to determine which ORPHA group codes to assign? For example, the patient presents diabetes, retinopathy, deafness, renal disease, cardiomiopathy... Could all the ORPHAs of these disease groups be assigned?

Because this is not the case of a confirmed diagnosis in which we only assign an ORPHAcode.

Kind regards,

María Elena

[MCecile-US14]

Dear Maria Elena,

Thank you for your request, I will add a specific post about ORPHA:616874 in the Wiki page in the coming days.

• First, could you please specify what "why ORPHAcoding" presentation you are refering to?

• From what I understand, I think there might be a confusion with terms here. In our recommendation slide provided in each training it is specified "Use the new code (ORPHA:616874 : Rare disorder without a determined diagnosis after full investigation), alone or in addition to the diagnostic assertion. Provide a phenotype and a genotype description of undiagnosed patients, moreover in registries." In our guidelines you can find here RD-CODE guidelines for coding undiagnosed patients, you can read details about ORPHA:616874 such as "A rare disorder for which all reasonable efforts have been done by rare diseases experts to determine a diagnosis according to the state of the art and available diagnostic capabilities, but did not enable to conclude on a clinically known concept. It is recommended to restrict the use of this entity for coding purpose to rare disease experts."

I would like to draw your attention that we recommend to specify or add extra comment in a free field of text or comment to keep informations or guide other investigation/patient registries as a phenotypic description, not an ORPHAcode assertion.

Most of the syndromes are multisystemic, In your case no group of disorders ORPHAcode should be used in addition with ORPHA:616874, it has to be used in specific cases and always stands alone as ORPHAcoding.

Please let me know if it is still unclear, Kind regards, Marie-Cécile

[Orphanet-ES]

Dear Marie-Cécile,

Regarding "why ORPHAcoding" presentation, I meant the one included in the Trainers-Toolkit: https://network.orphanet.org/ejprd_t14-1_trainers-toolkit/ Why ORPHAcoding slidedeck On the slide 29, the text in notes is: In the frame of the RD-CODE project, the best solution was to rely on the Orphanet classification that is currently implemented in the participating countries. Use of the Orphanet classification group levels (the higher up the lower the level of diagnosis definition).

Maybe this presentation is previous to the RD-CODE recommentations...

In any case, regarding the document RD-CODE guidelines for coding undiagnosed patients, in recommendation 3 it says: Additional phenotypic descriptors could be used (for instance ICD, SNOMED, Orphanet categories...)

And we understand that with Orphanet categories they mean the Orphanet groups of diseases. Could you clarify it?

Kind regards,

María Elena

[MCecile-US14]

Dear Maria Elena,

Thank you for the details. I could not find the notes in the 'Why ORPHAcoding' slidedeck but you are correct 'Orphanet categories' in the RD-CODE guidelines document and in this context does mean Orphanet 'Groups of disorders'. As I understood it and confirmed by @caterina-lucano-orphanet this was added in the 'additional phenotypic descriptors' potential list with ICD or SNOMED codes to be useful complementary informations in specific and exceptional cases (if certain and available). Indeed, as you know we strongly discouraged to use multiple ORPHAcodes to describe patients (except when a patient would be affected by 2 different rare diseases) but in some situation (e.g. unknown disease/syndrome with one meanly affected system) where you could raise attention toward a particular medical specialty by assigning its ORPHAcode group.

In this case, you are describing a multisystemic syndrome. Hence, it concerns a spectrum of symptoms affecting many anatomical or functional systems, which is justifying the use of ORPHA:616874 since up to now no clinically known disorder could be confirmed by a RD expert for this patient. So it does not make sense to suggest one group ORPHAcode because it wont be representative of the patient clinical presentation and not help future diagnosis (it can actually introduce more biass in interpretation). So in this situation it is a better to use ORPHA:616874 alone. Eventually complemented by other terminologies for clinical signs or phenotypical descriptors such as HPO terms.

Please, be cautious with these recommendations as you can understand it is really clinical situation-dependent and again ORPHA:616874 needs to be used with the maximum of precautions. You can always reference to the specific Wiki page about ORPHA:616874.

Let me know if extra clarifications are needed, Kind Regards, Marie-Cécile

[Orphanet-ES]

Thanks Marie-Cécile,

Much more clear now.

Kind regards,

María Elena