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NR 4-6/2008
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Alström syndrome – a
case report and literature review
Zespó³ Alströma – opis
przypadku i przegl±d literatury
Izabella Karska-Basta, Agnieszka
Kubicka-Trz±ska, Agnieszka Filemonowicz-Skoczek,
Bo¿ena Romanowska-Dixon, Joanna Kobylarz
Department of Ophthalmology, Clinic of Ophthalmology and Ocular
Oncology,
Jagiellonian University, Medical College, Kraków, Poland
Head: Ass. Prof. Bo¿ena Romanowska-Dixon, MD, PhD |
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| Summary: |
Purpose: To report
a case of Alström syndrome referred as bilateral macular
degeneration.
Material and methods: A 52 years old man was
diagnosed with an over 30 years history of progressive
visual acuity worsening in both eyes, with the presence
of night blindness and photophobia. Since childhood the
right eye has been positioned in a divergent deviation.
General history revealed: high grade obesity, dilated
cardiomyopathy with mitral insufficiency, diabetes
mellitus type 2, hepatic cirrhosis with elevated serum
enzymes, systemic hypertension. Family history: one
patient’s brother died at the age of 2 years because of
a congenital heart disease, and the second brother was
diagnosed for the congenital organic heart disease. The
basic ophthalmic examination was performed with
additional diagnostic methods including: kinetic visual
field examination, Amsler grid test, panel D-15 test,
fundus photography, ERG, EOG and VEP.
Results: Best corrected visual acuity of both
eyes was 0.1. Amsler grid and color vision tests were
normal. Visual field revealed concentric contraction in
both eyes. The funduscopy showed pale optic discs,
atrophic maculopathy, golden appearance of peripheral
and midperipheral fundus, coarser pigmentary changes
with a „bone-spicule” configuration and arterioral
narrowing. The red free pictures demonstrated the
atrophy of internal retinal layers and the infrared
pictures revealed the atrophy of the external layers of
the retina in posterior pole of the fundus. The flash
ERG showed reduced amplitude of photopic and scotopic
b-wave. The multifocal ERG demonstrated the normal
function of the central retina. EOG revealed decreased
Arden ratio in both eyes; 1.68 in the right and 1.32 in
the left. The pattern VEP revealed the P100 amplitude
reduction by 80% and elongation of latency by 120% in
the right eye and normal in the left eye. The flash VEP
showed normal latency and amplitude reduction by 50% in
both eyes.
Conclusions: Based on the results of performed
tests the diagnosis of Alström syndrome was established.
This rare congenital autosomal recessive condition is
characterized by progressive cone-rod retinal dystrophy
associated with obesity, sensorineural deafness, type 2
diabetes, congenital cardiac insufficiency secondary to
dilated cardiomyopathy, systemic hypertension and kidney
failure. |
| S³owa kluczowe: |
zespó³ Alströma, dystrofia
czopkowo-prêcikowa siatkówki, kardiomiopatia
rozstrzeniowa, oty³o¶æ, cukrzyca. |
| Key words: |
Alström syndrome, cone-rod
retinal dystrophy, dilated cardiomyopathy, obesity,
diabetes. |
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Alström syndrome is a very rare,
hereditary genetic disorder first described by Carl Henry
Alström in Sweden in 1959 (1). Currently about 450 individuals
diagnosed with Alström syndrome are known worldwide. It is an
autosomal recessive condition. The gene for Alström syndrome is
on chromosome 2 in band 2p13. Mutations in this gene which is
called ALMS1 lead to the production of an abnormal,
nonfunctional version of the ALMS1 protein, which is necessary
to maintain the integrity and the correct architecture of the
cellular membranes (2-4). The defect in such a protein could
account for the dysfunction involving many systems and/or
sensory organs. Wide clinical variability is observed among
affected individuals, including siblings. Alström syndrome is
characterized by cone-rod dystrophy, obesity, progressive
sensorineural hearing impairment, dilated cardiomyopathy and the
insulin resistance syndrome (5-9).
A case report
A 52 years old man was referred to our Retinal Diseases
Out-Patient Clinic with an over 30 years history of progressive
visual acuity worsening in both eyes with the presence of night
blindness, photophobia and horizontal nystagmus. The patient was
also complaining of visual field constriction, blurred and
distorted vision affecting near and far vision. The symptoms
affected activities of his daily life. General history and
examination revealed: high grade obesity (Fig. 1), dilated
cardiomyopathy with mitral valve insufficiency, diabetes
mellitus type 2, hepatic cirrhosis with elevated plasma ALT, AST,
GGT levels and systemic hypertension. Family history: one
patient’s brother died at the age of 2 years because of a
congenital heart disease, and the second brother was diagnosed
for the congenital organic heart disease.
The basic ophthalmic examination was performed with additional
diagnostic methods including: kinetic visual field examination,
Amsler grid test, panel D-15 test, electroretinogram (ERG),
electrooculogram (EOG) and visual evoke potentials (VEP).
Best corrected visual acuity in both eyes was 0.1. Amsler grid
and color vision tests revealed no abnormalities. Kinetic visual
field examination demonstrated a concentric contraction in both
eyes (Fig. 2a, 2b).
The funduscopy revealed pale optic discs, atrophic “bull-
eye” maculopathy (Fig. 3a, 3b), golden appearance of peripheral
and midperipheral fundus, coarser pigmentary changes with a „bone-spicule”
configuration with arterioral narrowing (Fig. 4a, 4b).
The red free pictures showed the atrophy of internal retinal
layers and the infrared pictures revealed the atrophy of the
external layers of the retina in the posterior pole of the
fundus (Fig. 5a, 5b and Fig. 6a, 6b).
The flash ERG showed reduced amplitude of photopic and scotopic
b-wave. The multifocal ERG demonstrated the normal function of
the central retina. EOG revealed decreased Arden ratio in both
eyes; 1.68 in the right and 1.32 in the left. The pattern VEP
showed reduction of the P100 amplitude by 80% and elongation of
its latency by 120% in the right eye and normal in the left eye.
The flash VEP revealed normal latency and amplitude reduction by
50% in both eyes.
Discussion
The earliest sign of Alstöm syndrome is often visual impairment
with photophobia and nystagmus as a result of a cone-rod
dystrophy which occurs in 100% of affected patients within the
first year of life (10,11). The retinal dystrophy progresses to
include the rods, with visual acuity of 6/60 or less by age of
ten years, increasing constriction of visual fields (8). An
atrophic “bull’s eye” maculopathy rarely occurs in Alström
syndrome (5). The electroretinogram is absent or attenuated with
better preserved rod than cone function. Rod function is
preserved initially but deteriorates as the individual ages.
Fundus examination in the first decade may be normal or may show
a pale optic disc and narrowing of the retinal vessels with
“bone-spicule” pigmentary changes (12). Posterior subcapsular
cataract is common. In literature there is also a report on an
Asian girl with bilateral congenital cone-rod dystrophy due to
Alström syndrome who developed subretinal exudation resembling
Coats’ disease (13). Another of the early signs may be dilated
cardiomyopathy (61%) and obesity (12,14,15). Multiple organ
systems later can be affected, resulting in hearing impairment
(81-88%), type 2 diabetes, heart failure, liver disease,
pulmonary fibrosis and renal failure. In our patient however no
hearing problems were noted. Additional features in some cases
include hypothyroidism, male hypogonadism, short stature and
mild to moderate developmental delay (25-30%) however the
majority of patients are of normal intelligence (5,7,16,17). The
complications of type 2 diabetes such as hyperlipidemia and
atherosclerosis may be observed (6).
Alström syndrome is associated with ALMS1 gene. Molecular
genetic testing of the ALMS1 gene is estimated to detect
mutations in 25%-40% of individuals (3,4). In our patient we did
not perform the genetic testing because they are not available
on a routine way. The diagnosis of Alström syndrome is based on
clinical findings but there is however considerable variation in
the clinical picture (6,7,16,17). The differential diagnosis of
Alström syndrome include: Bardet-Biedl syndrome, Leber’s
congenital amaurosis and achromatopsia (11,18-21). Bardet-Biedl
syndrome shares some features of Alström syndrome. The major
clinical features of Bardet-Biedl syndrome are rod-cone
dystrophy, postaxial polydactyly, central obesity, cognitive
impairment, hypogonadism, and renal dysfunction. A major
difference between Alström and Bardet-Biedl syndrome is the
timing of the onset of visual problems: in Alström syndrome,
visual problems are usually apparent in the first two years of
life; in Bardet-Biedl syndrome, the average age of onset of
visual problems is later in the first life decade (11).
Polydactyly, which is common in Bardet-Biedl syndrome, has not
been described in Alström syndrome. Mental retardation is well
described in Bardet-Biedl syndrome, while intellectual
dysfunction is less common in Alström syndrome. Other
differences include the relative infrequency of hearing problems,
which are observed in less than 5% of cases and diabetes
mellitus in 5-10% of patients with Bardet-Biedl syndrome.
Mutations in twelve different genes are associated with
Bardet-Biedl syndrome. Inheritance is autosomal recessive
(11,18). Leber congenital amaurosis is a severe dystrophy of the
retina without other organ system involvement, typically becomes
evident in the first year of life. Reduced vision is accompanied
by nystagmus, sluggish pupillary responses, photophobia,
hyperopia, and keratoconus. The ERG is characteristically
“nondetectable” or severely subnormal. Although the retina may
appear normal in infancy, a pigmentary retinopathy reminiscent
of retinitis pigmentosa is frequently observed later in
childhood. Eight genes currently known to be associated with
this disease: CRX, CRB1, GUCY2D, AIPL1, RDH12, RPGRIP1, RPE65,
and CEP290. Leber congenital amurosis is inherited in an
autosomal recessive manner, rarely in an autosomal dominant
manner (19). Achromatopsia a disorder that affects only the
retina and is characterized by reduced visual acuity, pendular
nystagmus, photophobia, a small central scotoma, eccentric
fixation, and reduced or complete loss of color discrimination.
Nystagmus and photophobia develop shortly after birth. Visual
acuity ranges from 20/200 or less in complete achromatopsia to
20/80 in incomplete achromatopsia (20). The diagnosis of
achromatopsia is based on color vision testing,
electrophysiologic examination. The fundus is usually normal.
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Mutations in three
genes, CNGA3, CNGB3, and GNAT2, are associated with this disease.
Inheritance is autosomal recessive (20,21,22).
In our case, the diagnosis of Alström syndrome has been made on
the precise evaluation of disease’s signs and symptoms. The
ophthalmologists were the first who established the diagnosis of
this rare condition. This rare congenital autosomal recessive
syndrome is characterized by progressive cone-rod retinal
dystrophy associated with obesity, type 2 diabetes, dilated
cardiomyopathy, sensorineural deafness, systemic hypertension
and kidney failure.
The paper was presented as a poster during
42 th Congress of Polish Ophthalmic Society
in Bydgoszcz, 20-23.06.2007.
Praca zosta³a zaprezentowana w formie plakatu
na 42. Zje¼dzie Polskiego Towarzystwa Okulistycznego w
Bydgoszczy w dniach 20-23.06.2007 r.
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degeneration combined with obesity, diabetes mellitus and
neurogenous deafness: a specific syndrome (not hitherto
described) distinct from the Laurence-Moon-Bardet-Biedl syndrome:
a clinical, endocrinological and genetic examination based on a
large pedigree. Acta Psychiatr Neurol. Scand Suppl 1959, 129, 1-
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three cases with further delineation of the clinical,
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Praca w³ynê³a do redakcji 12.12.2007 r. (1012)
Zakwalifikowano do druku 26.03.2008 r.
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Fig. 1. A 52 years old man with Alström
syndrome.
Ryc. 1. 52 letni mê¿czyzna z syndromem Alström’a.
Fig. 2a. Kinetic visual
field of the left eye.
Ryc. 2a. Kinetyczne pole widzenia oka lewego.
Fig. 2b. Kinetic visual
field of the right eye.
Ryc. 2b. Kinetyczne pole widzenia oka prawego.
Fig. 3a. Fundus retinography
showing atrophic bull’s eye maculopathy in the right eye.
Ryc. 3a. Makulopatie z zanikiem
typu „bawole oko” – oko prawe.
Fig. 3b. Fundus retinography
showing atrophic bull’s eye maculopathy in the left eye.
Ryc. 3b. Makulopatie z zanikiem
typu „bawole oko” – oko lewe.
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Fig. 4a. Picture of the midperiphery with
“bone-spicule” pigmentary changes of the fundus of the right eye.
Ryc. 4a. „Komórki kostne” na dnie
oka prawego.
Fig. 4b. Picture of the
midperiphery with “bone-spicule” pigmentary changes of the
fundus of the left eye.
Ryc. 4b. „Komórki kostne” na dnie oka lewego.
Fig. 5a. Red free picture of
the fundus of the right eye.
Ryc. 5a. Obraz „czerwonej plamki” na dnie oka prawego.
Fig. 5b. Red free picture of
the fundus of the left eye.
Ryc. 5b. Obraz „czerwonej plamki” na dnie oka lewego.
Fig. 6a. Infrared picture of
the fundus of the right eye.
Ryc. 6a. Dno oka prawego w ¶wietle bezczerwiennym.
Fig. 6b. Infrared picture of
the fundus of the left eye.
Ryc. 6b. Dno oka lewego w ¶wietle bezczerwiennym.
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