Rare Endocrinology News

Disease Profile

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

0

US Estimated

Europe Estimated

Age of onset

-

ICD-10

Q61.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

MCKD1; Medullary cystic kidney disease type 1; MUC1-related autosomal dominant medullary cystic kidney disease;

Categories

Kidney and Urinary Diseases

Summary

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is an inherited disorder that causes a gradual loss of kidney function. This may lead to the need for dialysis or kidney transplant usually between the ages of 30 and 70.[1][2] This condition is not associated with any symptoms outside of the kidney. ADTKD-MUC1 is caused by a mistake (mutation) in the MUC1 gene that leads to production of an abnormal mucin 1 protein, which deposits in the kidney and leads to slow loss of kidney function[3] ADTKD-MUC1 is inherited in families in an autosomal dominant pattern. It is diagnosed based on laboratory testing, family history and genetic testing. Kidney failure may be treated with dialysis and kidney transplant. ADTKD-MUC1 is very rare. Some patients may do well for a long time without any symptoms and may not require kidney transplant or dialysis until later in life.[1][2][3]

Symptoms

The symptoms of autosomal dominant tubulointerstitial kidney disease, due to MUC1 mutations (ADTKD-MUC1) are all related to chronic kidney disease. Kidney disease typically starts in the late teens to early 20s and gets worse until the kidneys stop working (end-stage renal disease). In early-stage chronic kidney disease, there are no symptoms. Laboratory testing may show an increase in serum creatinine. At a later stage, kidney disease may lead to high blood pressure, anemia, and gout. Gout is a painful arthritis due to high blood uric acid levels. In very advanced kidney disease (right before the need for dialysis or kidney transplant), patients can develop loss of appetite, nausea and fatigue.[1][2][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Anemia
Low number of red blood cells or hemoglobin
0001903
Autosomal dominant inheritance
0000006
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Decreased glomerular filtration rate
0012213
Elevated serum creatinine
Elevated creatinine
High blood creatinine level
Increased creatinine
Increased serum creatinine

[ more ]

 0003259
Glomerular sclerosis
0000096
Gout
0001997
Hypertension
0000822
Hyperuricemia
High blood uric acid level
0002149
Hypotension
Low blood pressure
0002615
Impaired renal uric acid clearance
0004732
Renal cortical atrophy
0002048
Renal corticomedullary cysts
0000108
Renal hypoplasia
Small kidneys
Underdeveloped kidneys

[ more ]

 0000089
Renal salt wasting
Loss of salt in urine
0000127
Renal tubular atrophy
0000092
Stage 5 chronic kidney disease
0003774
Tubular basement membrane disintegration
0005583
Tubulointerstitial fibrosis
0005576
Tubulointerstitial nephritis
0001970

Cause

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is caused by a mistake (mutation) in the MUC1 gene, which is responsible for making a protein called mucin 1. Mucin1 is involved in the growth and movement of cells, and in the development of the kidneys. In this condition, the mutation in the MUC1 gene leads to the creation of an abnormal MUC1 protein. This abnormal protein deposits within cells of the kidney and leads to slow break down of these cells and the loss of kidney function. While the abnormal protein is made throughout the body, it only causes problems in the kidney.[3]

Diagnosis

The diagnosis of autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is made based on an elevated creatinine level in the blood, a family history of kidney disease and genetic testing.[4][5] The urinalysis in patients with ADTKD-MUC1 usually shows no blood and very little protein, which is different from most types of kidney disease.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The treatment of autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is based on managing the symptoms. High blood pressure can be treated with medications. Anemia can be treated with the use of medications such as erythropoietin. Gout can be treated with the medications allopurinol or febuxostat. Eventually, patients may need a kidney transplant or dialysis. Live donor kidney transplantation is the optimal treatment for worsening kidney disease, and patients who undergo kidney transplant for this condition do extremely well. The condition does not come back in the transplanted kidney [4][5]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference contains information on Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations. This website is maintained by the National Library of Medicine.
        • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations. Click on the link to view a sample search on this topic.

            References

            1. Bleyer AJ, Kmoch S. Autosomal Dominant Tubulointerstitial Kidney Disease, MUC1-Related. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK153723/.
            2. Autosomal dominant tubule-interstitial kidney disease. National Organization for Rare Disorders (NORD). Updated 2017; https://rarediseases.org/rare-diseases/autosomal-dominant-interstitial-kidney-disease/.
            3. Medullary cystic kidney disease, type 1. Genetics Home Reference (GHR). Jun 2013; https://ghr.nlm.nih.gov/condition/medullary-cystic-kidney-disease.
            4. Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O. Kidney Disease: Improving Global Outcomes. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management-A KDIGO consensus report. Kidney Int. Oct 2015; 88(4):676-683. https://www.ncbi.nlm.nih.gov/pubmed/25738250.
            5. Bleyer A. Autosomal dominant tubulointerstitial kidney disease (medullary cystic kidney disease). UpToDate. Waltham, MA: UpToDate; Updated Dec. 5, 2018; https://www.uptodate.com/contents/autosomal-dominant-tubulointerstitial-kidney-disease-medullary-cystic-kidney-disease.

            Rare Endocrinology News