Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
1-1-2024
Journal
Kidney and Blood Pressure Research
DOI
10.1159/000539889
PMID
38901414
Abstract
Background: A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated autosomal dominant kidney hypomagnesemia with cardiomyopathy (ADKH-RRAGD). This disorder is characterized by renal loss of magnesium and potassium, coupled with varying degrees of cardiac dysfunction. These range from arrhythmias to severe dilated cardiomyopathy, which may require heart transplantation. Mutations associated with RRAGD significantly disrupt the non-canonical branch of the mechanistic target of rapamycin complex 1 pathway. This disruption hinders the nuclear translocation and transcriptional activity of the transcription factor EB a crucial regulator of lysosomal and autophagic function.
Summary: All identified RRAGD variants compromise kidney function, leading to hypomagnesemia and hypokalemia of various severity. The renal phenotype for most of the variants (i.e., S76L, I221K, P119R, P119L) typically manifests in the second decade of life occasionally preceded by childhood symptoms of dilated cardiomyopathy. In contrast, the P88L variant is associated to dilated cardiomyopathy manifesting in adulthood. To date, the T97P variant has not been linked to cardiac involvement. The most severe manifestations of ADKH-RRAGD, particularly concerning electrolyte imbalance and heart dysfunction requiring transplantation in childhood appear to be associated with the S76L, I221K, P119R variants.
Key messages: This review aimed to provide an overview of the clinical presentation for ADKH-RRAGD, aiming to enhance awareness, promote early diagnosis, and facilitate proper treatment. It also reports on the limited experience in patient management with diuretics, magnesium and potassium supplements, metformin, or calcineurin and SGLT2 inhibitors.
Keywords
Humans, Cardiomyopathies, Magnesium, Renal Tubular Transport, Inborn Errors, Hypokalemia, Cardiomyopathy, Hypokalemia, Hypomagnesemia, RRAGD, Tubulopathy
Published Open-Access
yes
Recommended Citation
Trepiccione, Francesco; Sambri, Irene; Ruggiero, Barbara; et al., "RRAGD-Associated Autosomal Dominant Kidney Hypomagnesemia with Cardiomyopathy: A Review on the Clinical Manifestations and Therapeutic Options" (2024). Duncan NRI Faculty and Staff Publications. 133.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/133
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