Renal disorders

Question 1

ALPORT SYNDROME AND THIN BM NEPHROPATHY

Responsible genes:
Proteins:
Cytogenetic loci:
Inheritance:
Clinical Features and Diagnostic Criteria:
Clinical Tests:
Molecular Tests:
Disease mechanism:
Treatment/Prognosis:

Answer 1

Responsible genes: XL: COL4A5, AR: COL4A3 and COL4A4, AD: COL4A3 and COL4A4
Proteins: Collagen alpha-3(IV) chain, Collagen alpha-4(IV) chain, Collagen alpha-5(IV) chain
Cytogenetic loci: 2q36-q37 (COL4A3 and COL4A4), Xq22.3 (COL4A5)
Inheritance: 80% X linked, 15% AR, 5% AD
Clinical Features and Diagnostic Criteria: Spectrum from progressive renal disease with cochlear and
ocular abnormalities (Alport) to isolated hematuria with a benign course (thin BM nephropathy).
Clinical Tests: Microhematuria, eventually proteinuria. Anterior lenticonus virtually pathognomonic, EM
on renal biopsy
Molecular Tests: Sequencing and deletion testing COL4A3, COL4A4, COL4A5 (80-100%)
Disease Mechanism: Type IV Collagen is found ubiquitously and is the major collagen component of
BMs. Alport due to abnl secretion of collagen alpha 3,4,and 5 (IV) chains
Treatment/Prognosis: ESRD: 60% by 30 yrs and 90% by 40 yrs and Deafness: 80-90% SN deafness
by age 40 in males, later in life in females with XL Alport. Renal progression and deafness is slower in
AD Alport and ocular lesions uncommon. Juvenile onset HL in AR Alport.