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Fanconi renotubular syndrome 5(FRTS5)

MedGen UID:
1711127
Concept ID:
C5394473
Disease or Syndrome
Synonym: FANCONI RENOTUBULAR SYNDROME, ACADIAN VARIANT
 
Gene (location): NDUFAF6 (8q22.1)
 
Monarch Initiative: MONDO:0030056
OMIM®: 618913

Definition

Fanconi renotubular syndrome-5 (FRTS5) is a mitochondrial disorder characterized by proximal renotubular dysfunction from birth, followed by progressive kidney disease and pulmonary fibrosis. It occurs only in individuals of Acadian descent (Crocker et al., 1997 and Hartmannova et al., 2016). For a discussion of genetic heterogeneity of Fanconi renotubular syndrome, see FRTS1 (134600). [from OMIM]

Clinical features

From HPO
Lung adenocarcinoma
MedGen UID:
57744
Concept ID:
C0152013
Neoplastic Process
A carcinoma that arises from the lung and is characterized by the presence of malignant glandular epithelial cells. There is a male predilection with a male to female ratio of 2:1. Usually lung adenocarcinoma is asymptomatic and is identified through screening studies or as an incidental radiologic finding. If clinical symptoms are present they include shortness of breath, cough, hemoptysis, chest pain, and fever. Tobacco smoke is a known risk factor.
Glycosuria
MedGen UID:
42267
Concept ID:
C0017979
Finding
An increased concentration of glucose in the urine.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Tubulointerstitial fibrosis
MedGen UID:
370652
Concept ID:
C1969372
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.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Hypophosphatemic rickets
MedGen UID:
309957
Concept ID:
C1704375
Disease or Syndrome
Rickets due to low serum phosphate concentrations, the cause of which can be nutritional or genetic. This condition is characterized by normal parathyroid hormone concentrations, usually caused by renal phosphate wasting occurring in isolation or as part of a renal tubular disorder, and characterized by resistance to treatment with ultraviolet radiation or vitamin D.
Emphysema
MedGen UID:
18764
Concept ID:
C0034067
Disease or Syndrome
A subcategory of chronic obstructive pulmonary disease (COPD). It occurs in people who smoke and suffer from chronic bronchitis. It is characterized by inflation of the alveoli, alveolar wall damage, and reduction in the number of alveoli, resulting in difficulty breathing.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Decreased DLCO
MedGen UID:
892993
Concept ID:
C4073175
Finding
Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test.
Hypophosphatemia
MedGen UID:
39327
Concept ID:
C0085682
Disease or Syndrome
An abnormally decreased phosphate concentration in the blood.
Hyperchloremic metabolic acidosis
MedGen UID:
369924
Concept ID:
C1969073
Disease or Syndrome
A form of metabolic acidosis with increased serum chloride levels.

Professional guidelines

PubMed

Wlodarski MW, Vlachos A, Farrar JE, Da Costa LM, Kattamis A, Dianzani I, Belendez C, Unal S, Tamary H, Pasauliene R, Pospisilova D, de la Fuente J, Iskander D, Wolfe L, Liu JM, Shimamura A, Albrecht K, Lausen B, Bechensteen AG, Tedgard U, Puzik A, Quarello P, Ramenghi U, Bartels M, Hengartner H, Farah RA, Al Saleh M, Hamidieh AA, Yang W, Ito E, Kook H, Ovsyannikova G, Kager L, Gleizes PE, Dalle JH, Strahm B, Niemeyer CM, Lipton JM, Leblanc TM; international Diamond-Blackfan anaemia syndrome guideline panel
Lancet Haematol 2024 May;11(5):e368-e382. doi: 10.1016/S2352-3026(24)00063-2. PMID: 38697731
Altintas B, Giri N, McReynolds LJ, Best A, Alter BP
Haematologica 2023 Jan 1;108(1):69-82. doi: 10.3324/haematol.2021.279981. PMID: 35417938Free PMC Article
Ring KL, Garcia C, Thomas MH, Modesitt SC
Am J Obstet Gynecol 2017 Nov;217(5):512-521. Epub 2017 Apr 12 doi: 10.1016/j.ajog.2017.04.011. PMID: 28411145

Recent clinical studies

Etiology

Altintas B, Giri N, McReynolds LJ, Best A, Alter BP
Haematologica 2023 Jan 1;108(1):69-82. doi: 10.3324/haematol.2021.279981. PMID: 35417938Free PMC Article
Zhang JM, Genois MM, Ouyang J, Lan L, Zou L
Mol Cell 2021 Mar 4;81(5):1027-1042.e4. Epub 2021 Jan 15 doi: 10.1016/j.molcel.2020.12.030. PMID: 33453166Free PMC Article
Karras GI, Yi S, Sahni N, Fischer M, Xie J, Vidal M, D'Andrea AD, Whitesell L, Lindquist S
Cell 2017 Feb 23;168(5):856-866.e12. Epub 2017 Feb 16 doi: 10.1016/j.cell.2017.01.023. PMID: 28215707Free PMC Article
Mendoza O, Bourdoncle A, Boulé JB, Brosh RM Jr, Mergny JL
Nucleic Acids Res 2016 Mar 18;44(5):1989-2006. Epub 2016 Feb 15 doi: 10.1093/nar/gkw079. PMID: 26883636Free PMC Article
Nowell PC
Cancer Genet Cytogenet 1982 Mar;5(3):265-78. doi: 10.1016/0165-4608(82)90034-6. PMID: 7039817

Diagnosis

Wlodarski MW, Vlachos A, Farrar JE, Da Costa LM, Kattamis A, Dianzani I, Belendez C, Unal S, Tamary H, Pasauliene R, Pospisilova D, de la Fuente J, Iskander D, Wolfe L, Liu JM, Shimamura A, Albrecht K, Lausen B, Bechensteen AG, Tedgard U, Puzik A, Quarello P, Ramenghi U, Bartels M, Hengartner H, Farah RA, Al Saleh M, Hamidieh AA, Yang W, Ito E, Kook H, Ovsyannikova G, Kager L, Gleizes PE, Dalle JH, Strahm B, Niemeyer CM, Lipton JM, Leblanc TM; international Diamond-Blackfan anaemia syndrome guideline panel
Lancet Haematol 2024 May;11(5):e368-e382. doi: 10.1016/S2352-3026(24)00063-2. PMID: 38697731
Taylor AMR, Rothblum-Oviatt C, Ellis NA, Hickson ID, Meyer S, Crawford TO, Smogorzewska A, Pietrucha B, Weemaes C, Stewart GS
Nat Rev Dis Primers 2019 Sep 19;5(1):64. doi: 10.1038/s41572-019-0113-0. PMID: 31537806Free PMC Article
Karras GI, Yi S, Sahni N, Fischer M, Xie J, Vidal M, D'Andrea AD, Whitesell L, Lindquist S
Cell 2017 Feb 23;168(5):856-866.e12. Epub 2017 Feb 16 doi: 10.1016/j.cell.2017.01.023. PMID: 28215707Free PMC Article
Shao C, Wang Y, Gao Y
Sci China Life Sci 2011 May;54(5):409-17. Epub 2011 Mar 31 doi: 10.1007/s11427-011-4162-1. PMID: 21455690
Loi M
Orphanet J Rare Dis 2006 May 18;1:16. doi: 10.1186/1750-1172-1-16. PMID: 16722554Free PMC Article

Therapy

Campbell L, Barbini B, Cromarty B, Hamzah L, Williams D, Winston A, Post FA; FANTA trial team
AIDS 2024 Jul 15;38(9):1442-1445. Epub 2024 Jun 27 doi: 10.1097/QAD.0000000000003916. PMID: 38932750
Fraj A, El Euch M, Jaziri F, Kefi A, Abdelghani KB, Turki S, Abdallah TB
Saudi J Kidney Dis Transpl 2020 Sep-Oct;31(5):1144-1147. doi: 10.4103/1319-2442.301185. PMID: 33229783
Rochowski A, Olson SB, Alonzo TA, Gerbing RB, Lange BJ, Alter BP
Pediatr Blood Cancer 2012 Nov;59(5):922-4. Epub 2012 Apr 19 doi: 10.1002/pbc.24168. PMID: 22517793Free PMC Article
Viganò M, Lampertico P, Colombo M
Expert Opin Drug Saf 2011 Sep;10(5):809-18. Epub 2011 Jun 15 doi: 10.1517/14740338.2011.593507. PMID: 21671843
Gil HW, Yang JO, Lee EY, Hong SY
Nephrology (Carlton) 2005 Oct;10(5):430-2. doi: 10.1111/j.1440-1797.2005.00437.x. PMID: 16221089

Prognosis

Karras GI, Yi S, Sahni N, Fischer M, Xie J, Vidal M, D'Andrea AD, Whitesell L, Lindquist S
Cell 2017 Feb 23;168(5):856-866.e12. Epub 2017 Feb 16 doi: 10.1016/j.cell.2017.01.023. PMID: 28215707Free PMC Article
Devuyst O, Thakker RV
Orphanet J Rare Dis 2010 Oct 14;5:28. doi: 10.1186/1750-1172-5-28. PMID: 20946626Free PMC Article
Loi M
Orphanet J Rare Dis 2006 May 18;1:16. doi: 10.1186/1750-1172-1-16. PMID: 16722554Free PMC Article
Cox H, Viljoen D, Versfeld G, Beighton P
Clin Genet 1989 May;35(5):322-30. doi: 10.1111/j.1399-0004.1989.tb02952.x. PMID: 2788043
Nowell PC
Cancer Genet Cytogenet 1982 Mar;5(3):265-78. doi: 10.1016/0165-4608(82)90034-6. PMID: 7039817

Clinical prediction guides

Kurian AW, Ward KC, Abrahamse P, Hamilton AS, Katz SJ
JNCI Cancer Spectr 2021 Feb;5(1) Epub 2020 Sep 18 doi: 10.1093/jncics/pkaa083. PMID: 33426465Free PMC Article
Shimizu M, Furusyo N, Ikezaki H, Ogawa E, Hayashi T, Ihara T, Harada Y, Toyoda K, Murata M, Hayashi J
World J Gastroenterol 2015 Feb 21;21(7):2116-23. doi: 10.3748/wjg.v21.i7.2116. PMID: 25717246Free PMC Article
Stoepker C, Faramarz A, Rooimans MA, van Mil SE, Balk JA, Velleuer E, Ameziane N, Te Riele H, de Winter JP
DNA Repair (Amst) 2015 Feb;26:54-64. Epub 2014 Dec 24 doi: 10.1016/j.dnarep.2014.12.003. PMID: 25583207
Watanabe T, Matsuda T, Kitagata R, Tajima I, Ono H, Hirano K, Shirai M, Endoh A, Hongo T
Pediatr Int 2014 Oct;56(5):e68-71. doi: 10.1111/ped.12412. PMID: 25336014
Rochowski A, Olson SB, Alonzo TA, Gerbing RB, Lange BJ, Alter BP
Pediatr Blood Cancer 2012 Nov;59(5):922-4. Epub 2012 Apr 19 doi: 10.1002/pbc.24168. PMID: 22517793Free PMC Article

Recent systematic reviews

Dos Santos ES, Pérez-de-Oliveira ME, Normando AGC, Gueiros LAM, Rogatto SR, Vargas PA, Lopes MA, da Silva Guerra EN, Leme AFP, Santos-Silva AR
Head Neck 2022 Dec;44(12):2925-2937. Epub 2022 Sep 16 doi: 10.1002/hed.27193. PMID: 36114663

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