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Rare and metabolic

Educational resources for renal medicine

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Rare diseases affecting the kidney

An approach with a few examples, prepared for the UK Renal Association's  Advanced Nephrology Course. By Clinical features of a handful of selected conditions in the pdf at the foot of the page.

When you don't know | when you do | Fabry disease | Other conditions | Other resources | Downloads

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What to use when you don't know the diagnosis 

Links show sample search "gout kidney disease genetic":

  • Dr Google - 'oldest and best' (estab. 1997) Can be remarkably effective.  
  • - intellectual Google, links to papers etc. 
  • PubMed - one of the astonishingly good free resources from NCBI (US). They've changed the world of science and medicine. Publicly funded for the benefit of the world by US taxes in a foresightful, liberating move - " thanks Obama*" (*actually 1988, the Reagan era; history). Register and log in automatically each time you visit for additional features. 
  • OMIM - Online Mendelian Inheritance in Man, one of many alternatives on the PubMed drop-down menu
  • Professor Wikipedia - particularly good on genes and genetics. Usual cautions apply. Have you thought about editing it?


When you do know the diagnosis:

  • - diseases listed if there is a UK expert group and a Register. UK-relevant info about how to get testing done, management pathways.  Great resource. Use it! Register your patients on Radar, become the local link?
  • Gene Reviews (NCBI) many of these are outstanding, as good as many text books.  There are exceptions, and not all diseases are covered. 
  • Gene Cards are technical but useful.
  • For patients,  Genetics Home Reference (NIH) has good concise explanations, but tends to be quite dry. For professionals, often provides a good intro to complex topics.
  • There may be good professional or patient sites on specific conditions, and some of these can be exceptional.

See for instance this Fabry example:

(Anderson-) Fabry Disease

a-galactosidase deficiency leads to accumulation of glycoshpingolipid in lysosomes, primarily of endothelial cells.  An important disease to diagnose, as now treatable by enzyme replacement, and a good example of the issues in managing lysosomal disorders, metabolic diseases, etc.

The  UK management guidelines 2012 from the now-defunct NHS Specialist Services, downloadable at the foot of this page, give an thorough guide to diagnosis and management, though some screening seems over the top and they need updating. Useful info in Gene Reviews (NCBI) on Fabry. There are UK centres for Fabry Disease in London (Royal Free/UCL, GOSH), Salford, Birmingham (QE and BCH), Cambridge, but probably a need for more, or for a second tier of more local clinicians who are familiar with the condition.

Fabry is usually cared for by specialists in Metabolic Medicine in the UK.  Most come from a Chemical Pathology background and don't have inpatient beds.  The patients have diseases in many systems and local management is essential too. Some have significant or end stage renal disease.  Nephrologists may be key providers and coordinators of care for many. They could play a role in conditions too, maybe. ( Metabolic Medicine curriculum)

Some other conditions

Features of some of these summarised in the pdf dowloadable at the foot

Tuberous sclerosis Autosomal dominant disease (TSC1 and 2 encoding hamartin, tuberin) causing lumps in brain, kidneys, skin (adenoma sebaceum), and in women, lung. Kidneys predominantly may become replaced, or develop large angiomyolipomas.  They may have some cysts, or in a minority masses of cysts because of contiguous genes PKD1/TSC2. Viewing images in Radiopaedia is recommended. There is a very good  Wikipedia page on Tuberous Sclerosis and for an advanced view, the Gene Review on TS is the place to go.  The molecular basis of TS is uncontrolled activation of mTOR.  So inhibitors of mTOR (sirolimus, everolimus etc) seem a natural therapeutic avenue.  A little more info on clinical details in the pdf at the foot of the page
Birt Hogg Dube syndrome Facial lesions can resemble Tuberous Sclerosis; renal oncocytomas; pneumothoraces.  AD, variable features.  Top quality info at
LCAT deficiency Very rare autosomal recessive disorder causes loss of lecithin-cholesterol acyl transferase.  Leads to accumulation of lipid deposits in cornea, glomerulus, and low HDL; cloudy cornea (fish eyes) and progressive proteinuric kidney disease seems common in complete deficiency. The best intro to this fascinating but complex disorder is Genetics Home Reference, GHR on LCAT deficiency and also read GHR on partial LCAT deficiency which gives more molecular background. Autoimmune-caused enzyme deficiency has also been reported. gives an unusually good summary.
Methylmalonic acidaemia Also known as methylmalonic aciduria. In addition to the metabolic manifestations (), causes interstitial renal disease, which often leads to ESRF and transplantation. There's a good Gene Review on MMA
Nail patella syndrome Autosomal dominant condition in which mutations in the transcription factor LMX1B cause a series of features with considerable variation even within families.  The characteristic nail and skeletal abnormalities are sometimes accompanied by proteinuric renal disease which may lead to ESRF; but LMX1B mutations are now being identified in patients with familial renal disease but without the characteristic non-renal features.  The Gene Review on NPS is typically good, led by Liverpool geneticist Elizabeth Sweeney, who has contributed patient and professional info at NPS UK. A little info more concisely in the pdf at the foot of this page
Von Hippel Lindau A complex topic and the Genetics Home Reference (GHR) page on VHL is a good intro. There is a very good Gene Review on VHL.  The pathogenesis involves HIF (Hypoxia-inducible factor).  


Additional resources

  • - the Rare Renal initiative of the Renal Assoc and BAPN provides info on clinical pathways and how to get advice for the UK. It oversees the renal rare disease registries (Radar). 
  • has good info on these conditions, mostly in Section 15 on Genetic Disease. But it's not free, and we have to declare an interest, low-level financial as well as ensuring that the content is excellent. (The Oxford Textbook of Clinical Nephrology - eUpdates annually)

Finally some recommended resources on other things

  • Try any of our other  edrep resources  
  • Our patient info and unit protocols are at
  • Radiopaedia has thousands of radiological images for your free re-use with attribution

This page written by Neil Turner @neilturn  Date of last update shown in footer.

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Page last modified 07.01.2019, 11:26 by Administrator. edrep and edren are produced by the Renal Unit at the Royal Infirmary of Edinburgh and Univ. Edinburgh. CAUTIONS and Contact us. Note that the information published here is primarily intended for education, not for clinical care.