inherited dosroders Flashcards
polycystic kidney disease is what
autosom dom predom variant
auto rec
adpkd
most frequent life-threatening hereditary kidney disease
adpkd mutations
pkd gene1 (85% cases on chromosome16)
pkd2 (15% cases on chromosome4)
pkd1 develope end stage kidney failure EARLIER
pathology of adpkd
massive cyst enlargement-large kidneys
epithelial lined cysts from small pop renal tubules
(25% of kidneys) benign adenomas
clin fts adpkd
reduce urine conc ability
chronic pain
hypertension common early (31yrs mean)
haematuria - cyst rupture, cystitis, stones
cyst infection
renal failure
extra renal clin features
HEPATIC CYSTS
mc extra renal manifestation
liver cysts present 10yrs after renal cysts
liver function generally preserved
can result in SOB, pain, ankle swelling
INTRA CRANIAL ANEURYSMS
4-8%pts
seen in clusters of fam membs
mainly in ant. circulation terriroty
screening indiciated in patients w/ fh
more extra renal !
CARDIAC
mitral/aortic valve prolapse
valvular disease - collagenous/myxomatous degeneration
DIVERTICULAR
increased prevalence and complications -ots on dialysis
diverticulitis & colonic perforation -2 serious comps
HERNIAS
increased incidnece of abdominal/inguinal herniams (45%)
diagnosing adpkd
RADIOLOGICAL:
US presence of multiple bilateral cysts
renal enlargment
CT/MRI when unclear on USS
GENETIC:
linkage analysis
mutation analysis
adpkd children
early onset in uteri or first yr life
siblings inc risk of early disease
similar renal involv as adults
single cyst in high risk pts enough for dx
cerebral aneurysms rare in children
diff to distinguish from arpkd - uss suggests congenital hepatic fibrosis (suggesting recessive dis)
genetic pattern adpkd
offspring of affected = 50% risk of having disease
management adpkd
hypertension-rigorous control
hydration
proteinuria reduction
cyst haemorrhage+ cyst infection
new treatment:
reduce cyst volume and progression – Tolvaptan (ADH (AVP) receptor antagonist)
renal failure:
dialysis
transplant
cv and cerebrovasc causes- death
auto rec kidney disease
mainly young child affected and assoc w/ hepatic lesions
rare (1/20 000)
pkdh1 gene chrom6
renal involvement bilateral symmetrical
generally normal urinary tract
histologically cysts seen appearing from collecting duct system
(involvement may be 30-90% of ducts depending on severity)
clin pres aRpkd
varies and depens on renal/liver lesions
relevance is diff between severe forms and neonatal period survival
kidney palpable always
hypertension
recurrent UTIs
slow decline in GFR (less than 1/3 reach dialysis)
ARPKD prognosis
30 - 50% children affected SEVERE
infants who survive neonate 9-24% survive year 1
cjildren who survive year 1 have 80% prob over 15yrs
acquired cystic disease (radiology app.)
multiple parapelvic cysts of right kidney seen on US or excretory urogram
alports (hereditary nephritis)
1-2%pts w/ ESRD
x linkied inheritance (85%)
disorder of type IV collagen matrix
mutation in COL4A5 gene leads to deficient collagenous matrix deposition
manifestation of alports
haematuria (classic fature)
proteinuria later but thats bad progn
EXTRA RENAL
(sensorineural deafness, ocular defects-anterior lenticonus, leiomyomatosis of oesophagus/genitalia-rare)
diagnosing alports
suspect w/ microscopic haematuria +-hearing loss
renal biopsy (varible thickness GBM - classic)
thickening of GBM w/ splitting of lamina densa electron microscopy
alport treatment
no specif
standard treat BP, proteinuria
dialysis/transplant
anderson fabrys
inborn error of Glycosphingolipid metabolism (deficiency of a-galactosidase A)
x linked disease lysosomal storage disease
affects kidneys, liver,lungs,erythrocytes
uncommon
clinical features of anderson fabrys
renal failure
cutaneous- angiokeratomas
cardiac- cardiomyopathy,valvular disease
neuro-stroke,acroparaesthesia
psych
diagnosis fabrys
plasma/leukocyte a-GAL activity
renal biopsy
skin biopsy
(shows concentric lamellar inclusion within lysosymes)
treating fabrys
enzyme replacement-fabryzyme
managing complications
medullary cystic kidney
rare inherited cystic disease (auto dom)
morphologically abnormal renal tubules leading to fibrosis
affected - normal/small kidneys
cysts in corticomedullary junction/medulla
