Biology Reference
In-Depth Information
at least 1% of congenital hearing loss (Gorline et al. 1995). Alport syn-
drome has significant clinical and genetic heterogeneity, with most cases
demonstrating X-linked dominant inheritance, while others appear to be
autosomal recessive. In general, females are less affected than males in X-
linked Alport cases, whereas the sexes are equally affected in autosomal
forms. The age of onset and severity of disease are variable in both auto-
somal and X-linked forms.
The nephritis of Alport syndrome is heralded by the presence of blood
in the urine. Light-microscopic evaluation demonstrates nonspecific
changes in the kidneys, and ultrastructural examination reveals splitting of
the glomerular basement membrane with irregular thickening or thinning.
Early studies revealed absence of type IV collagen subunits in affected
glomerular basement membranes, implicating it in the disease process (Jeraj
et al. 1983). The nephritis of Alport syndrome may progress to renal failure
and death (Flinter 1993).
The sensorineural hearing loss is bilateral, progressive, and variable in
severity (Gleeson 1984). Up to 55% of males and 40% of females will
develop hearing loss (Cassady 1966; Chiricosta et al. 1970). The onset
is typically during the second decade of life, and high frequencies are
predominantly affected (Rintelmann 1976). Speech audiometry and other
audiologic tests suggest that the primary defect resides within the cochlea
(Miller et al. 1970). Vestibular responses may be mildly reduced in some
cases (Celis-Blaubach et al. 1974; Gleeson 1984; Miller et al. 1970).
Histopathologic examinations of affected temporal bones have revealed
nonspecific and inconsistent results that cannot distinguish cochlear pathol-
ogy secondary to renal dysfunction from cochlear pathology occurring con-
comitantly with renal dysfunction (Schuknecht 1993).
The hypothesis that the cochlea and kidney may share a common path-
ogenic mechanism in Alport syndrome arises from the observation that they
appear to share some antigenic, ultrastructural, and physiologic features.
Perhaps the most notable similarity is their microvasculature and its asso-
ciated basement-membrane structures that are highly specialized for the
critical microfiltration processes in kidney glomeruli and the stria vascularis
of the inner ear. Alternatively, the observed auditory system pathology
may be secondary to kidney failure associated with increased levels of
cochleotoxic factors in the blood. These factors may be endogenous meta-
bolites, or exogenous factors commonly used to treat Alport syndrome
patients, including ototoxic drugs such as aminoglycoside antibiotics and
diuretics. Hemodialysis is another common therapy for the kidney failure
of Alport syndrome and is associated with sensorineural hearing loss (Rizvi
and Holmes 1980). It is therefore difficult to discern which cochlear patho-
logic changes are directly caused by the primary disease process, and which
are secondary to kidney failure and its therapies.
