Autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease

1. AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE (ARPKD) SUNIL KUMAR.P Haematology & Transfusion Medicine 2/16/2018 1 SUNIL KUMAR.P

2. Introduction Definition Epidemiology Etiology – Genetic Pathogenesis Clinical features Morphological features Diagnosis 2/16/2018 2 SUNIL KUMAR.P

3. INTRODUCTION The infantile (AR) form of polycystic kidney disease (ARPKD) is distinct from the adult form. ARPKD is less common. Incidence : 1:20,000 births. It is transmitted as an autosomal recessive trait & family H/o of similar disease is not present. 2/16/2018 3 SUNIL KUMAR.P

4. DEFINITION ARPKD is the recessive form of PKD. It is associated with a group of congenital fibrocystic syndromes. Mutations in the PKHD1 (chromosomal locus 6p12.2) cause ARPKD. 2/16/2018 4 SUNIL KUMAR.P

5. Epidemiology: Inherited disorder – progressive enlargement of renal collecting ducts varying degrees of hepatic abnormality Rare 1:10,000 to 1:40,000 Caucasians > other ethnic groups? 2/16/2018 5 SUNIL KUMAR.P

6. Genetics AR Mutation in PKHD1, chromosome 6P21 Encodes for polyductin / fibrocystin protein This protein is localised in primary cilia mainly in the kidney To lesser extent in liver, pancrease and arterial wall. 2/16/2018 6 SUNIL KUMAR.P

7. Pathogenesis The condition occurs due to a mutation in chromosome 6p21 , PKHD1 (polycystic kidney and hepatic disease). It is invariably bilateral. The age at presentation may be perinatal , neonatal, infantile or juvenile. ….But frequently serious manifestations are present at birth and result in death from renal failure in early childhood. 2/16/2018 7 SUNIL KUMAR.P

8. Clinical features: Flank masses HTN Urinary concentration defect Hyponatraemia Renal insufficiency Pulmonary hypoplasia Oesophageal varices hyperspleenism 2/16/2018 8 SUNIL KUMAR.P

9. Morphologic Features Gross Findings : The kidneys are bilaterally enlarged with smooth external surface and reniform shape. C/s- reveals small, fusiform or cylindrical cysts radiating from medulla to cortex. Kidneys – sponge like appearance 2/16/2018 9 SUNIL KUMAR.P

10. Microscopic findings : The total No. of nephrons is normal. Collecting tubules show cylindrical or saccular dilatations & are lined by cuboidal to low columnar epithelium. Glomeruli – shows cystically dilated. 2/16/2018 10 SUNIL KUMAR.P

11. Diagnosis US features typical of ARPKD( enlarged,ecchogenic kidneys with poor CMD and clinical, lab or radiological evidence of hepatic Fibrosis hepatic pathology demonstrating ductal plate abnormality previous affected sibling parental consanguinity suggestive of AR inheritance 2/16/2018 11 SUNIL KUMAR.P

12. Genetic testing is typically not required for patient with classic ARPKD Prenatal diagnosis in a family with at least one affected child via mutation analysis With identification and cloning of PKHD1 molecular analysis is now available 2/16/2018 12 SUNIL KUMAR.P

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