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Familial juvenile hyperuricemic nephropathy type 2(ADTKD4)

MedGen UID:
Concept ID:
Disease or Syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Gene (location): REN (1q32.1)
Monarch Initiative: MONDO:0013128
OMIM®: 613092
Orphanet: ORPHA217330

Disease characteristics

The two clinical presentations observed in autosomal dominant tubulointerstitial kidney disease – REN (ADTKD-REN) correlate with the renin protein domains affected by the causative REN variants. Childhood/adolescent onset, the more common presentation (caused by REN variants encoding the signal peptide or prosegment domains), is characterized by decreased estimated glomerular filtration rate, acidosis, hyperkalemia, and anemia early in life, followed by slowly progressive chronic kidney disease (CKD) and gout. Adult onset, the less common presentation (caused by REN variants encoding the mature renin peptide), is characterized by gout or mild slowly progressive CKD, beginning in the third decade. Anemia, hyperkalemia, and acidemia do not occur. [from GeneReviews]
Martina Živná  |  Kendrah Kidd  |  Stanislav Kmoch, et. al.   view full author information

Additional descriptions

Autosomal dominant tubulointerstitial kidney disease-4 (ADTKD4) is a progressive renal disorder characterized by early-onset anemia and increased serum uric acid with a bland urinalysis and without proteinuria. Although the anemia tends to improve with age, progressive renal insufficiency results in end-stage kidney disease between 40 and 70 years. Renal ultrasound may show small echogenic kidneys, and biopsy shows tubular atrophy and interstitial fibrosis, sometimes with cysts and secondary glomerulosclerosis (summary by Zivna et al., 2009). For discussion of the revised nomenclature and genetic heterogeneity of ADTKD, see ADTKD1 (162000).  http://www.omim.org/entry/613092
From MedlinePlus Genetics
REN-related kidney disease is an inherited condition that affects kidney function. This condition causes slowly progressive kidney disease that usually becomes apparent during childhood. As this condition progresses, the kidneys become less able to filter fluids and waste products from the body, resulting in kidney failure. Individuals with REN-related kidney disease typically require dialysis (to remove wastes from the blood) or a kidney transplant between ages 40 and 70.

People with REN-related kidney disease sometimes have low blood pressure. They may also have mildly increased levels of potassium in their blood (hyperkalemia). In childhood, people with REN-related kidney disease develop a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue. In this disorder, anemia is usually mild and begins to improve during adolescence.

Many individuals with this condition develop high blood levels of a waste product called uric acid. Normally, the kidneys remove uric acid from the blood and transfer it to urine so it can be excreted from the body. In REN-related kidney disease, the kidneys are unable to remove uric acid from the blood effectively. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. Individuals with REN-related kidney disease may begin to experience the signs and symptoms of gout during their twenties.  https://medlineplus.gov/genetics/condition/ren-related-kidney-disease

Clinical features

From HPO
Focal segmental glomerulosclerosis
MedGen UID:
Concept ID:
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
MedGen UID:
Concept ID:
Increased levels of protein in the urine.
Renal hypoplasia
MedGen UID:
Concept ID:
Congenital Abnormality
Hypoplasia of the kidney.
Chronic kidney disease
MedGen UID:
Concept ID:
Disease or Syndrome
Functional anomaly of the kidney persisting for at least three months.
Renal tubular atrophy
MedGen UID:
Concept ID:
The presence of renal tubules with thick redundant basement membranes, or a reduction of greater than 50% in tubular diameter compared to surrounding non-atrophic tubules.
Tubulointerstitial fibrosis
MedGen UID:
Concept ID:
Disease or Syndrome
A progressive detrimental connective tissue deposition (fibrosis) on the kidney parenchyma involving the tubules and interstitial tissue of the kidney. Tubulointerstitial injury in the kidney is complex, involving a number of independent and overlapping cellular and molecular pathways, with renal interstitial fibrosis and tubular atrophy (IF/TA) as the final common pathway. However, IF and TA are separable, as shown by the profound TA in renal artery stenosis, which characteristically has little or no fibrosis (or inflammation). For new annotations it is preferable to annotate to the specific HPO terms for Renal interstitial fibrosis and/or Renal tubular atrophy.
Hyperechogenic kidneys
MedGen UID:
Concept ID:
An increase in amplitude of waves returned in ultrasonography of the kidney, which is generally displayed as increased brightness of the signal.
MedGen UID:
Concept ID:
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
MedGen UID:
Concept ID:
Disease or Syndrome
An abnormally high level of uric acid in the blood.

Term Hierarchy

Follow this link to review classifications for Familial juvenile hyperuricemic nephropathy type 2 in Orphanet.

Professional guidelines


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
Kidney Int 2015 Oct;88(4):676-83. Epub 2015 Mar 4 doi: 10.1038/ki.2015.28. PMID: 25738250

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