AS is a genetically heterogeneous disorder that developed from mutations in the genetic encoding alpha-3, alpha-4, & alpha-5(IV) chains of type IV col
Clinical manifestations, diagnosis, & treatment of Alport syndrome (AS) (hereditary nephritis)
AS is a genetically heterogeneous disorder that developed from mutations in the genetic encoding alpha-3, alpha-4, & alpha-5(IV) chains of type IV collagen, & could be transmitted in an X-linked, autosomal recessive, or autosomal dominant pattern.
Clinical features & Dgx
(1) Alterations of the alpha-3, alpha-4, or alpha-5(IV) chains of type IV collagen causing basement membrane glomerular changes, ocular, and inner ear leading to appearance of the clinical findings of AS.
(2) Classic presentation of AS is relying primarily upon the clinical manifestations of the involved males with X-linked disorder. These manifestations may include glomerular disease that can progress to ESRD, ocular abnormalities (e.g., anterior lenticonus), sensorineural hearing loss with +ve family history of renal failure & hearing loss.
(3) Ptns presenting with autosomal recessive disorder have similar clinical features and behaviour as those with X-linked disease, whereas ptns with autosomal dominant pattern generally show a slower decline in renal function and are less likely to show sensorineural deafness & ocular alterations.
(4) The first renal manifestation of AS is often a symptomless microscopic haematuria. Gross haematuria, however, may also be a presenting finding that may be seen after an upper respiratory tract infection. The SCr & BP are normal in early childhood, but progressive renal dysfunction, HT, and increased proteinuria progress with time. ESRD can be currently observed between 16 & 35 years old, but the course is more indolent in certain families.
(5) Females with X-linked AS are heterozygous for genetic mutations and have certain clinical findings due to lyonization that only one X chromosome is active per cell.
(6) Dgx is made by molecular genetic analysis (if cost is not matter), or skin or kidney biopsy with characteristic criteria of AS.
Therapy of Alport syndrome:
(1) There’s no specific therapy to manage the underlying genetic error of AS.
(2) In ptns with Alport disease + overt proteinuria, RAAS blockade therapy decrease the rate of the urinary protein excretion in addition to impede the progression of the disease process. Consequently, an annual follow up monitoring of proteinuria is advised once AS has been diagnosed. Therapy with an ACEi or an ARB to any ptn presented with Alport disease + overt proteinuria. It is also accepted to consider an angiotensin blockade therapy in those ptns presenting with microalbuminuria but still not yet showing overt proteinuria.
(3) CyA (cyclosporine) administration is not currently advised in ptns with AS. CyA has not been proved to limit the rate of renal disease progression and has evident SE that include CyA-induced renal toxicity.
(4) Either modality, DX or KTx can be performed in ptns with AS complicated by ESRD.
(5) The preferrable RRT modality is KTx. Recurrence of AS did not reported in the allograft (donor glomerular basement membrane [GBM] is currently normal); however, about 3 % of Tx men may develop de novo anti-GBM AB disease.
Living-related (LR) donors: Since AS is a familial disorder, potential LR donors for AS ptns must be carefully assessed.
v Male relatives of a ptn with X-linked AS with NO haematuria are 👉 suitable donors.
v Women who are heterozygous for X-linked AS should NOT be a donor unless:
1) She’s aSymtic with no haematuria (about 5 % of individuals) & understands and accepts that there’s a 50 % risk of transmitted mutation with each pregnancy. This = if she donates to a male relative prior to childbearing, she could not donate to an affected son who hs not yet bn born within donation time.
2) She is > 45 ys with normal urinary protein + normal hearing “audiogram”, + normal kidney function. However, she is the lastly resorted donor.
Male & female who is heterozygous for COL4A3 or COL4A4 mutation may be 👉suitable donor to an autosomal recessive AS recipient, if showed normal urinary protein & renal function. But, if the heterozygous state observed with CKD/ESRD, donation will NOT be feasible.
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