UGE2: Arvelige sygdomme

Question 1

Hvilken er den hyppigste arvelige nyresygdom?

Answer 1

Autosomal Dominant Polycystic Kidney Disesase ADPKD

Hyppigste arvelige nyresygdom (1:1000)

Question 2

Hvordan er arvgangen og genetiken bag ADPKD?

Answer 2

• 50 % risiko for nedarvning af sygdom
• Hver familie ofte unik mutation
• Afficerede gener er PKD1 (85 %) og PKD2 (15%)
• Kendetegnes ved langsomt progredierende cystisk forstørrelse af nyrer hvilket fører til hypertension, progredierende nyresvigt → ESRD
• Kun få nefroner afficeres (1-5 %)
• 10-15 % negativ familianamnese

Question 3

Hvordan manifesterer sig ADPKD?

Answer 3

•Kliniske fænotype for PKD1 og PKD2 ens, men senere debut for PKD2
–Nyrecyster
–Levercyster
–Intrakranielle aneurismer
•Manifesterer sig typisk i 40-60 årsalder
•Hyppig årsag til ESRD. 6% af de der påbegynder dialyse/TX
•Ingen specific behandling/helbredelse (Tolvaptan )
•Generaliseret bindevævsdefekt

Question 4

Hvordan stilles diagnosen ADPKD?

Answer 4

• Ultralydsskanning (anden billeddiagnostik)
• Ved behov genetisk udredning
• Fremtid genetisk screening i forhold til risiko-stratificering og mulig fremtidig behandling

Question 5

Hvad er Pei-kriterierne?

Answer 5

Ultralydsdiagnostiske kriterier for ADPKD (for genetisk disposinerede)
15-39 år: Fund af 3 eller flere cyster unilateralt eller bilateralt
40-59 år: Fund af 2 eller flere cyster i hver nyre
>60 år: Fund af 4 eller flere cyster i hver nyre
(alder ved diagnos vs antal cyster ved UL)

Question 6

Er det muligt at lave en pre-natal diagnose af ADPKD?

Answer 6

Ja. De som ses har oftare en mer aggressiv variant af ADPKD.

Question 7

Hvordan behandlar man ADPKD?

Answer 7

Hypertension
Blod lipider
Smerter
Infektion, i og udenfor urinveje, i cyster
Aneurysmer
Dialyse og transplantation: 
–Evt prætx nefrektomi
–Nyrer
–Evt komb levertx (kvinder)

Question 8

Hvilke komorbiditeter ses ved ADPKD?

Answer 8

Cerebrale aneurysmer! 10-15%
•Screening anbefales hos ALLE APKD patienter med positiv SAH familie anamnese
Levercyster
Mitral prolaps
Colon divertikler
Hernier
Smerter
Arteriosclerose
Hypertension

Question 9

Hvordan foregår rådgivningen for ADPKD?

Answer 9

• Børn, familiemedlemmer der bør undersøges
• Forsikring
• Antihypertensiv beh.
• Dialyse/transplantation
• Screening for cerebrale aneurismer
• Gentest kan tilbydes

Question 10

Hvilke sygdomme hör under hereditäre hematurier?

Answer 10

Alport’s syndrome (AS)
Thin Basement Membrane Disease
Alias COLA4 diseases

Question 11

Hvordan diagnostiserer man Alports syndrome?

Answer 11

• Hudbiopsi
• Nyrebiopsi
• Genetisk testning

Question 12

Hvad karakteriserer X linked Alports syndrome?

Answer 12

• Der forekommer ikke far til søn transmission
• Proteinuri plus hæmaturi hos kvinder
• Langsom fald i GFR
• Drenge mere afficerede

Question 13

Hvor har man mutationer i TBMD?

Answer 13

Mutations in one COL4A3 or A4 allele

Question 14

Hvor har man mutationer i AS?

Answer 14

• X-linked 60%, mutations in COL4A5 on the X chromosome
• Autosomal recessive 15%, mutations in COL4A3 or COL4A4 genes
• Autosomal dominant 20 %, heterocygotes mutations in COL4A3 or COL4A4 genes biopsy

Question 15

Hvad menes med at TBMD er carriers of AS?

Answer 15

Patients with TBMN can be considered “carriers” of autosomal recessive Alport syndrome since mutations in both alleles of COL4A3 or COL4A4 cause autosomal recessive Alport syndrome. Mutations in both alleles can be the same (homozygous) or different (compound heterozygous). Approximately 40 to 50 percent of heterozygous carriers of a COL4A3 or COL4A4 mutation in Alport families exhibit microhematuria.

Question 16

Hvorfor får man hematorui i TBMD selvom man kun har 1 allele?

Answer 16

Although both alleles of COL4A3 or COL4A4 must be involved to produce autosomal recessive Alport syndrome, TBMN is transmitted in a dominant fashion because the abnormal gene product produces a defect in collagen that is sufficiently severe to interfere with the normal architecture of glomerular basement membranes, resulting in hematuria. In most cases, however, the heterozygous defect does not provoke the secondary processes that result in the proteinuria, impaired glomerular filtration, and renal fibrosis observed in patients with Alport syndrome.

Question 17

Hvilke sygdommer skal man taenke på når det er en patient med persisterende glomulär hematuri?

Answer 17

•Alport
–Positiv familieanamnese med hæmaturi associeret med nyresvigt og høretab
•IgA nefritis
–Negativ familieanamnese
•Tynd basalmembransyndrom
–Positiv familieanamnese med hæmaturi
–Negativ familieanamnese med nyresvigt og høretab

Question 18

Hvordan presenterer sig den typiske patient hos AS?

Answer 18

Typical patient: deaf male with hematuria at age 10 and renal failure at age 15 to 35
•The tempo of progressive renal dysfunction depends, at least in part, upon the underlying mutation.

Question 19

Hvad kalles TBMD og AS sammen?

Answer 19

The spectrum of disorders encompassing TBMN and Alport syndrome has been called the Collagen IV Nephropathies.
•Patients with TBMN can be considered “carriers” of autosomal recessive Alport syndrome since mutations in both alleles of COL4A3 or COL4A4 cause autosomal recessive Alport syndrome.

Question 20

Hvilke organsystemer udover nyrerne er påvirket i AS?

Answer 20

Hearing loss—Bilateral sensorineural hearing loss is a common feature in patients with Alport syndrome [15]. Hearing loss begins in the high frequency range and progresses over time to frequencies in the range of conversational speech.
Ocular manifestations
Anterior lenticonus is a regular conical protrusion on the anterior aspect of the lens due to thinning of the lens capsule. Retinal changes of bilateral white or yellow granulations superficially located in the retina surrounding the foveal areas are specific for Alport syndrome.
Corneal changes are nonspecific findings and include posterior polymorphous dystrophy and recurrent corneal erosion, which can cause severe ocular pain

Question 21

Hvilken af TBMD og AS er hyppigst?

Answer 21

TBMD: incidence: 1:20 HYPPIGST
AS: Incidence 1:50.000.

Question 22

Hvad er forskelle mellem AS og TBMD?

Answer 22

AS:
Progressive
X-linked >85%
Deafness
Autosomal rec.
Autosomal dom.
Renal biopsy 
Genetic exam

TBMD:
Stable renal function *
< 1.5 g dU-protein
Autosomal dominant 
Renal biopsy not indicated