Congenital Diarrhea and Enteropathies in Infants: Approach to Diagnosis

Mantoo, Mohsin Raj; Malik, Rohan; Das, Prasenjit; Yadav, Rajni; Nakra, Tripti; Chouhan, Pandu

doi:10.1007/s12098-021-03844-z

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Although manifestations of CODE gene variants are often present in the neonatal period, until recently, many infants did not receive a definitive genetic diagnosis due to a lack of availability and awareness around appropriate genetic testing. The advent of low-cost whole exome and genome sequencing (WES/WGS) and gradually increased recognition of these disorders by pediatric medical practitioners has led to considerable advances in diagnosis and the identification of the causative gene variants ( Elkadri, 2020 ; Mantoo et al, 2021 ; Russo, 2020 ; Thiagarajah et al, 2018 ; Younis et al, 2020 ). With rapid clinical exome sequencing now available in many pediatric medical centers, the numbers of causative genes and types of gene variants have quickly expanded.…”

Section: Introductionmentioning

confidence: 99%

Modeling the cell biology of monogenetic intestinal epithelial disorders

Kaji,

Thiagarajah,

Goldenring

2024

Journal of Cell Biology

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Monogenetic variants are responsible for a range of congenital human diseases. Variants in genes that are important for intestinal epithelial function cause a group of disorders characterized by severe diarrhea and loss of nutrient absorption called congenital diarrheas and enteropathies (CODEs). CODE-causing genes include nutrient transporters, enzymes, structural proteins, and vesicular trafficking proteins in intestinal epithelial cells. Several severe CODE disorders result from the loss-of-function in key regulators of polarized endocytic trafficking such as the motor protein, Myosin VB (MYO5B), as well as STX3, STXBP2, and UNC45A. Investigations of the cell biology and pathophysiology following loss-of-function in these genes have led to an increased understanding of both homeostatic and pathological vesicular trafficking in intestinal epithelial cells. Modeling different CODEs through investigation of changes in patient tissues, coupled with the development of animal models and patient-derived enteroids, has provided critical insights into the enterocyte differentiation and function. Linking basic knowledge of cell biology with the phenotype of specific patient variants is a key step in developing effective treatments for rare monogenetic diseases. This knowledge can also be applied more broadly to our understanding of common epithelial disorders.

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Section: Introductionmentioning

confidence: 99%

Modeling the cell biology of monogenetic intestinal epithelial disorders

Kaji,

Thiagarajah,

Goldenring

2024

Journal of Cell Biology

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“…Evaluation of CoDE disorders: The diagnostic evaluation of CoDE disorders has evolved considerably over the past few years with the advent of accessible genetic testing and gradual increased recognition of these disorders by pediatric medical practitioners. General diagnostic approaches have emerged over the past few years to aid in the initial evaluation for infants with suspected CoDEs (Thiagarajah et al 2018 ; Elkadri 2020 ; Younis et al 2020 ; Russo 2020 ; Mantoo et al 2021 ). In summary, most approaches focus on identification of infants with a history and symptoms suspicious for a CoDE disorder, initial dietary and stool evaluation, early genetic testing, and endoscopic biopsy evaluation as soon as safely possible.…”

Section: Introductionmentioning

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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