• About
  • Masthead
  • License Content
  • Advertise
  • Submit Press Release
  • RSS/Email List
  • 2MM Podcast
  • Write for us
  • Contact Us
2 Minute Medicine
No Result
View All Result

No products in the cart.

SUBSCRIBE
  • Specialties
    • All Specialties, All Recent Reports
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Pharma
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • AI Roundup
  • Pharma
  • The Scan+
  • Classics™+
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Podcasts
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account
2 Minute Medicine
  • Specialties
    • All Specialties, All Recent Reports
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Pharma
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • AI Roundup
  • Pharma
  • The Scan+
  • Classics™+
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Podcasts
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account
SUBSCRIBE
2 Minute Medicine
Subscribe
Home All Specialties Chronic Disease

Mitochondrial dysfunction identified in the pathogenesis of renal Fanconi’s syndrome

bys25qthea
January 9, 2014
in Chronic Disease, Genetics
Reading Time: 3 mins read
0
Share on FacebookShare on Twitter

Image: PD 

1. A missense mutation in the gene encoding the enzyme, EHHADH was identified in all members of a family diagnosed with isolated Fanconi’s syndrome (dysfunction of renal proximal tubular cells). 

2. This mutation was responsible for the mistargeting of peroxisomal EHHADH, resulting in mitochondrial dysfunction. 

Study Rundown: The proximal tubule is a highly metabolically active segment of the nephron; dysfunction of this segment (such as in renal Fanconi’s syndrome) may cause life-threatening metabolic abnormalities and loss of nutrients. Fanconi’s syndrome can be “acquired” whereby systemic disease results in direct proximal tubular damage or, in rare cases, “isolated” in which the pathogenesis remains unknown. Mitochondrial dysfunction has been a proposed mechanism for isolated Fanconi’s syndrome since the proximal tubule is known to be a metabolically active area.

Using gene sequencing of a family with isolated Fanconi’s syndrome as well as mouse models and biochemical studies, this study was the first to demonstrate that a single missense mutation (located on chromosome 3q27) leads to a structural change in the protein EHHADH, which normally localizes to peroxisomes. Mutated EHHADH was then shown to incorrectly bind to mitochondrial targets (HADHA and HADHB), leading to impaired cellular respiration and subsequent dysfunction of proximal tubular cells.

A limitation of this study includes the applicability of the results (i.e. molecular targets) as all human participants for the genome study were from the same family with known isolated Fanconi’s syndrome. However, as technology improves and with our advancing knowledge in pathogenesis of specific conditions, the wider implication of this study is the possibility for molecular screening in the future as more targets continue to be elucidated.

RELATED REPORTS

Whole exome sequencing effective at identifying mitochondrial pathogenic mutations

Click to read the study, published today in NEJM

In-Depth: Eighteen members of one black family (nine members with Fanconi’s syndrome) were enrolled into the study. Genomewide linkage analysis and gene sequencing identified a single heterozygous missense mutation in EHHADH which occurred in all affected family members. Urine metabolite analysis also demonstrated a unique profile when comparing Fanconi’s versus non-Fanconi’s syndrome family members. Cell-based studies (transfection of model proximal tubular cells with normal versus mutant EHHADH) demonstrated mutant EHHADH localization to mitochondria and a defect in the transepithelial transport of fluids – both of which were not seen in cells with normal EHHADH. Measurement of mitochondrial respiratory function also confirmed reduced energy production in mutant EHHADH transfected cells. Finally, complete knockout of EHHADH in mice had no significant effect on urinary electrolyte excretion or metabolites, indicating that mistargeting of mutant EHHADH to mitochondria is the pathogenetic mechanism.

By Jonathan Liu, MD and Adrienne Cheung

More from this author: SSRI use during pregnancy not linked to increased risk of autism Combo antifungal therapy most effective treatment for cryptococcal meningitis, Rhinovirus, genes may interact to increase risk of childhood asthma, Functional MRI map for physical pain identified Glutamine and antioxidant supplementation provide no benefit for critically-ill patients New Hepatitis C virus (HCV) treatment effective  

©2012-2014 2minutemedicine.com. All rights reserved. No works may be reproduced without expressed written consent from 2minutemedicine.com. Disclaimer: We present factual information directly from peer reviewed medical journals. No post should be construed as medical advice and is not intended as such by the authors, editors, staff or by 2minutemedicine.com. PLEASE SEE A HEALTHCARE PROVIDER IN YOUR AREA IF YOU SEEK MEDICAL ADVICE OF ANY SORT.  

Tags: Fanconimitochondria
Previous Post

Tight glycemic control in pediatric ICU does not reduce mortality

Next Post

Preoperative low-dose steroids sufficient for steroid-treated IBD

RelatedReports

BRAF V600E mutations linked with increased mortality in thyroid cancer
Chronic Disease

Whole exome sequencing effective at identifying mitochondrial pathogenic mutations

July 2, 2014
Next Post
Thalidomide may be effective in refractory pediatric Crohn’s disease

Preoperative low-dose steroids sufficient for steroid-treated IBD

Number of lives saved due to tobacco control continues to rise

Number of lives saved due to tobacco control continues to rise

Artificial surfactant linked to significant improvement of RDS [Pediatrics Classics Series]

2 Minute Medicine® is an award winning, physician-run, expert medical media company. Our content is curated, written and edited by practicing health professionals who have clinical and scientific expertise in their field of reporting. Our editorial management team is comprised of highly-trained MD physicians. Join numerous brands, companies, and hospitals who trust our licensed content.

Recent Reports

  • #VisualAbstract: Obicetrapib Reduced LDL Cholesterol in Patients at High Cardiovascular Risk
  • St. Louis hospital-based violence intervention program did not significantly affect reinjury outcomes
  • Glucagon-like peptide-1 receptor agonists may increase risk of reflux in patients with type 2 diabetes
License Content
Terms of Use | Disclaimer
Cookie Policy
Privacy Statement (EU)
Disclaimer

© 2021 2 Minute Medicine, Inc. - Physician-written medical news.

  • Specialties
    • All Specialties, All Recent Reports
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Pharma
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • AI Roundup
  • Pharma
  • The Scan
  • Classics™
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Podcasts
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account
No Result
View All Result

© 2021 2 Minute Medicine, Inc. - Physician-written medical news.