Chylomicron retention disease caused by a new pathogenic variant in sar1b protein: a rare case report from Syria

Doya, Leen Jamel; Mohammad, Lava; Omran, Razan; Ibrahim, Alexander; Yousef, Nizar; Ibrahim, Ali; Houreih, Mohammad Adib

doi:10.1186/s12887-021-02897-5

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…The in-frame deletion p.Ser117_Lys160del eliminates a long portion of the protein, including an important binding site for GTP (Jones et al 2003 ). The p.Glu114del mutation produces CRD by removing a single glutamic acid residue, but the mechanism of this mutation’s pathology remains uncertain (Doya et al 2021 ). Missense mutations which have been identified include p.Gly37Arg, which removes a key glycine in the GxxxxGKT motif, and p.Gly185Val, which removes a structurally important glycine at the beginning of an alpha helix (Jones et al 2003 ; Peotter et al 2019 ).…”

Section: Enzymes and Metabolismmentioning

confidence: 99%

The genetics of monogenic intestinal epithelial disorders

2022

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Monogenic intestinal epithelial disorders, also known as congenital diarrheas and enteropathies (CoDEs), are a group of rare diseases that result from mutations in genes that primarily affect intestinal epithelial cell function. Patients with CoDE disorders generally present with infantile-onset diarrhea and poor growth, and often require intensive fluid and nutritional management. CoDE disorders can be classified into several categories that relate to broad areas of epithelial function, structure, and development. The advent of accessible and low-cost genetic sequencing has accelerated discovery in the field with over 45 different genes now associated with CoDE disorders. Despite this increasing knowledge in the causal genetics of disease, the underlying cellular pathophysiology remains incompletely understood for many disorders. Consequently, clinical management options for CoDE disorders are currently limited and there is an urgent need for new and disorder-specific therapies. In this review, we provide a general overview of CoDE disorders, including a historical perspective of the field and relationship to other monogenic disorders of the intestine. We describe the genetics, clinical presentation, and known pathophysiology for specific disorders. Lastly, we describe the major challenges relating to CoDE disorders, briefly outline key areas that need further study, and provide a perspective on the future genetic and therapeutic landscape.

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Section: Enzymes and Metabolismmentioning

confidence: 99%

The genetics of monogenic intestinal epithelial disorders

2022

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Chylomicron retention disease: a rare aetiology of failure to thrive

Sunkoj,

Yu,

Altaf

et al. 2024

BMJ Case Rep

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The aetiology of failure to thrive (FTT) in children is broad, of which some conditions are extremely rare. It is important to consider these rarer conditions, especially in the setting of other concerning signs/symptoms or when there is no improvement with conventional treatment. In this case report we highlight such a rare condition—chylomicron retention disease (CRD) as an aetiology of FTT. CRD often presents with non-specific symptoms, resulting in delayed diagnosis which is established by genetic workup and histology from small intestinal biopsies. Despite being rare, CRD needs to be considered as one of the differential diagnoses after ruling out the more common causes of FTT.

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Unraveling Chylomicron Retention Disease Enhances Insight into SAR1B GTPase Functions and Mechanisms of Actions, While Shedding Light of Intracellular Chylomicron Trafficking

Levy,

Fallet-Bianco,

Auclair

et al. 2024

Biomedicines

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Over the past three decades, significant efforts have been focused on unraveling congenital intestinal disorders that disrupt the absorption of dietary lipids and fat-soluble vitamins. The primary goal has been to gain deeper insights into intra-enterocyte sites, molecular steps, and crucial proteins/regulatory pathways involved, while simultaneously identifying novel therapeutic targets and diagnostic tools. This research not only delves into specific and rare malabsorptive conditions, such as chylomicron retention disease (CRD), but also contributes to our understanding of normal physiology through the utilization of cutting-edge cellular and animal models alongside advanced research methodologies. This review elucidates how modern techniques have facilitated the decoding of CRD gene defects, the identification of dysfunctional cellular processes, disease regulatory mechanisms, and the essential role of coat protein complex II-coated vesicles and cargo receptors in chylomicron trafficking and endoplasmic reticulum (ER) exit sites. Moreover, experimental approaches have shed light on the multifaceted functions of SAR1B GTPase, wherein loss-of-function mutations not only predispose individuals to CRD but also exacerbate oxidative stress, inflammation, and ER stress, potentially contributing to clinical complications associated with CRD. In addition to dissecting the primary disease pathology, genetically modified animal models have emerged as invaluable assets in exploring various ancillary aspects, including responses to environmental challenges such as dietary alterations, gender-specific disparities in disease onset and progression, and embryonic lethality or developmental abnormalities. In summary, this comprehensive review provides an in-depth and contemporary analysis of CRD, offering a meticulous examination of the CRD current landscape by synthesizing the latest research findings and advancements in the field.

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Chylomicron retention disease caused by a new pathogenic variant in sar1b protein: a rare case report from Syria

Cited by 3 publications

References 9 publications

The genetics of monogenic intestinal epithelial disorders

The genetics of monogenic intestinal epithelial disorders

Chylomicron retention disease: a rare aetiology of failure to thrive

Unraveling Chylomicron Retention Disease Enhances Insight into SAR1B GTPase Functions and Mechanisms of Actions, While Shedding Light of Intracellular Chylomicron Trafficking

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