SDS & Science Snapshots (2022-07-03)

In this issue: IRDiRC Working Group Recommendations for rare disease patients; The Access to Rare Indications Act could be a game changer for millions of Americans; New Case Report from Romania on Novel Biallelic Variants in DNAJC21.

Welcome to our weekly updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email or message us on Facebook! This is all for you!

Recommendations from the IRDiRC Working Group on methodologies to assess the impact of diagnoses and therapies on rare disease patients

The IRDiRC Working group recently published an article making recommendations for improving treatments for rare disease patients. In 2017 the International Rare Diseases Research Consortium (IRDiRC) set its 10-year goal to “Enable all people living with a rare disease to receive an accurate diagnosis, care, and available therapy within one year of coming to medical attention.” The authors acknowledge that in order for this goal to be met, there must be transparency about the impact of every step of the diagnostic and therapeutic journey on patients’ lives. Their recommendations range from information that should be assessed by clinicians, healthcare providers, and insurance companies to more comprehensively care for rare disease communities.

“The goal many of us working in research have, is to help these rare disease patients and families solve some of the greatest challenges in receiving a proper diagnosis and treatment plan for a rare disease,” said David A. Pearce in IRDiRC's recent press release. “The work done by this workgroup recommends new metrics for the development of new tools to ensure more accurate diagnosis and to assess the impact of therapies and diagnosis on rare disease patients.”

In the article the abstract summarized their finding: "Rare disease patients face many challenges including diagnostic delay, misdiagnosis and lack of therapies. However, early access to diagnosis and therapies can modify the management and the progression of diseases, which in return positively impacts patients, families and health care systems. The International Rare Diseases Research Consortium set up the multi-stakeholder Working Group on developing methodologies to assess the impact of diagnoses and therapies on rare disease patients. Using the patients’ journey on the diagnostic paradigm, the Working Group characterized a set of metrics, tools and needs required for appropriate data collection and establishment of a framework of methodologies to analyze the socio-economic burden of rare diseases on patients, families and health care systems. These recommendations are intended to facilitate the development of methodologies and to better assess the societal impact of rare diseases."

The Access to Rare Indications Act could be a game changer for millions of Americans

The Access to Rare Indications Act, introduced to Congress in late 2021, aims at addressing a common challenge for rare disease patients: the off-label use of medication.

Because rare diseases often lack approved therapeutics, clinicians often rely on the use of drugs approved for other disorders to manage symptoms. So what is the problem? You guessed it: the cost that falls on patients and families. Off-label use of medication can become prohibitive because it is not always covered by insurance companies. Overcoming this barrier by covering off-label drug use for rare disease patients is a crucial step in making therapies more accessible.

In a New Case Report from Romania, Clinicians report Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype, and provide a comprehensive review of other cases reported in the literature.

The authors refer to the disorder as "bone marrow failure syndrome type 3", but some consider it an "SDS-like" syndrome, as we discussed recently in an other Snapshot post:

In addition to a very detailed case report, the authors summarize and compare the findings of 17 other patients with biallelic variants in DNAJC21, and highlight in their discussion the challenges and importance of timely genetic diagnosis.

"Bone marrow failure syndromes represent a diverse group of hematological disorders implicating single-line cytopenia or pancytopenia that may lead to the indication for hematopoietic stem cell transplantation (Bluteau et al., 2018). They may be acquired or inherited. Recognizing the inherited nature of bone marrow failure is crucial to prevent inappropriate treatment with immunosuppressant agents and to offer hematopoietic stem cell transplant with an adapted regimen, when needed. Importantly, identifying the genetic cause will help select the healthy donor and provide genetic counseling to the family (Barhoom et al., 2021). Even more, understanding the genetic cause may improve the management of several associated syndromic features. This patient had a late molecular diagnosis that led to some unnecessary treatments, such as cow milk protein restriction for 1 y and 6 months. In addition, the family had another child where informed genetic counseling was not possible in the absence of a molecular diagnosis. Fortunately, none of the siblings carry the variants.

The DNAJC21 gene was first associated with bone marrow syndrome type 3 in the year 2016 (Tummala et al., 2016). This is one of the reasons why despite several genetic tests performed, a diagnosis was not established for this child. Panels performed did not include the DNAJC21 gene, while the exome analysis did not identify the two variants in DNAJC21 to be associated with bone marrow failure. Genome sequencing performed in 2020 aimed to evaluate variants that could have been missed by the exome sequencing; however, it revealed the two exonic variants in the DNAJC21 gene, at the time recognized to cause disease, thus showing the importance of automated reinterpretation of negative exomes. Even more, there are probably other unknown genes that cause bone marrow failure, as suggested by other authors (Tummala et al., 2016; Dhanraj et al., 2017)."

Read the full article, below.

Case Report: Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis.

Chirita-Emandi A, Petrescu CA, Zimbru CG, Stoica F, Marian C, Ciubotaru A, Bataneant M, Puiu M.Front Genet. 2022 Apr 8;13:870233.

doi: 10.3389/fgene.2022.870233. eCollection 2022.

PMID: 35464845

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