Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations

Other Names: MCKD1; Medullary cystic kidney disease type 1; MUC1-related autosomal dominant medullary cystic kidney disease; MUCI-related ADTKD; MUC1-related autosomal dominant tubulointerstitial kidney disease; Medullary cystic kidney disease 1 (former); Mucin-1 kidney disease; ADTKD due to MUC1 mutations; ADTKD-MUC1; Autosomal dominant tubulointerstitial kidney disease, MUC1-associated

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.

Epidemiology

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is very rare and has been reported in about 100 families in the US.

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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) is inherited in an autosomal dominant pattern. All individuals inherit two copies of each gene.

In autosomal dominant conditions, having a mutation in just one copy of the associated (MUC1) gene causes the person to have the disease. Some people are born with an autosomal dominant condition due to a new genetic mutation (de novo) and do not have a history of this condition in their family, although this is very rare in ADTKD-MUC1. There is nothing either parent can do, before or during pregnancy, to cause a child to have this. Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the MUC1 mutation and ADTKD-MUC1. Offspring who inherit the MUC1 mutation will have ADTKD-MUC1. The age of onset of kidney failure may be different between an affected parent and their children.

Signs and 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. This condition is not associated with any symptoms outside of the kidney.

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. The urinalysis in patients with ADTKD-MUC1 usually shows no blood and very little protein, which is different from most types of kidney disease.

Renal ultrasound examination may reveal normal or small kidneys. Renal biopsy findings are nonspecific (and, hence, not diagnostic). Identification of a heterozygous MUC1 pathogenic variant on molecular genetic testing confirms the diagnosis.

Treatment

Treatment follows standard guidelines for chronic kidney disease (CKD) and its sequelae, which can include hypertension, anemia, and gout. Affected individuals are encouraged to prepare for kidney transplantation, the definitive treatment of ADTKD-MUC1, by staying in optimal health (e.g., by exercising, avoiding obesity and tobacco usage, and maintaining strict control of hypertension, dyslipidemia, and other cardiovascular risk factors). Transplantation is curative, and the outcome from kidney transplantation in this group of patients is excellent.

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.

Prognosis

The long-term outlook for people with autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADKTD-MUC1) is good, though patients will often need a kidney transplant or start dialysis between the ages of 30 and 70. At this point, it is difficult to predict at what age patients will develop end-stage kidney failure.

NIH genetic and rare disease info

• NIH info on Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations

Autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations is a rare disease.

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