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Anterior Segment Cornea
Ocular Features of Treatable Lysosomal Storage Disorders –
Fabry Disease, Mucopolysaccharidoses I, II and VI and Gaucher Disease
a report by
Ines M Lanzl
1
and Bart P Leroy
2
1. Department of Ophthalmology, Munich University of Technology; 2. Department of Ophthalmology and Centre for Medical Genetics, Ghent University Hospital
Lysosomal storage disorders (LSDs) are a group of more than 50 inheritable acroparesthaesia (constant burning or tingling in the extremities) and
disorders.
1,2
Although individually rare, they collectively affect approximately acute, episodic pain attacks originating from the hands and feet triggered
one in 5,000 live births.
3
Defective metabolism of proteins, carbohydrates or by illness, exercise, fever, stress or weather changes. As the disease
lipids resulting from deficiency of one of the many lysosomal enzymes leads progresses, life expectancy is substantially decreased by renal
to pathological accumulation of substances within the lysosomes. This dysfunction, cardiac complications and cerebral involvement.
9,13
Kidney
lysosomal accumulation triggers an insidious cascade of processes generally involvement manifests as albuminuria/proteinuria and impaired
leading to progressive tissue damage and organ failure. glomerular filtration rate as early as in the second decade of life, and
patients typically progress to end-stage renal disease in their 40s. Cardiac
Most physicians have difficulty recognising patients in an early stage of the complications include left ventricular hypertrophy, arrhythmias, valvular
disease, as each patient is unique in terms of age of presentation, cluster of abnormalities, myocardial infarction and cardiac failure. Central nervous
presenting symptoms, rate of disease progression and co-morbidities. system complications may include transient ischaemic attacks and early
Symptoms may initially seem harmless and may be suspected to be due to stroke. In heterozygous females, the disease spectrum spans from
another, more common disease.
4
Hence, valuable time may elapse before absence of symptoms to classic Fabry disease with severe renal, cardiac
the patient is diagnosed and considered for therapeutic intervention with and/or neurological complications. As the initial Fabry symptoms can
enzyme-replacement therapy (ERT), if available for that particular disorder.
5
mimic those of more common disorders, many patients are not
With age, progression of the disease generally has a strong impact on the diagnosed until adulthood and, on average, there is a delay of a decade
health and quality of life of affected patients, and life-threatening or more between symptom onset and diagnosis.
14,15
complications significantly reduce life expectancy.
1,5
Ocular Features
The early signs and symptoms of LSDs can include pathognomonic
ophthalmic features.
6–8
It is thus imperative that ophthalmologists are Cornea
familiar with these signs, even if they will encounter such an LSD patient Distinctive corneal opacities play an important role in the early detection and
maybe only once during their ophthalmic career. In this article, we will diagnosis of Fabry disease as they are reported to be present almost
describe the disease characteristics and ocular features of five LSDs that universally among male Fabry patients and in a high proportion (>70%) of
are currently treatable with ERT: Fabry disease, mucopolysaccharidosis heterozygous females.
16,17
In some cases they cause light sensitivity.
18,19
In
(MPS) types I, II and VI and Gaucher disease. the absence of retinal vascular occlusion and ischaemic optic neuropathy,
visual acuity is typically not impaired. In the early stages, the opacities appear
Fabry Disease as a fine haze that is mostly diffuse and involves the whole cornea.
20,21
Fabry disease is a life-threatening LSD characterised by a deficient activity
of the lysosomal enzyme α-galactosidase A.
9
This deficiency results in a
Ines M Lanzl works in the Department of Ophthalmology
diminished ability to catabolise certain glycolipids. Progressive lysosomal
at the Technical University Hospital in Munich (TUM). Her
accumulation of undegraded globotriaosylceramide (GL-3) occurs in
research topics include ocular blood circulation and
many cell types throughout the body, e.g. in vascular endothelial cells,
glaucoma, and she is the author or co-author of over 50
peer-reviewed publications. After completing her training
connective tissue, kidneys, heart, brain, nerves and cornea. The initial in ophthalmology at the TUM, Dr Lanzl specialised further
insult of substrate accumulation leads to secondary tissue damage and
and was a clinical as well as a research glaucoma fellow
at Wills Eye Hospital in Philadelphia, and an anterior
irreversible organ failure in a cascade of overlapping steps.
10
Fabry disease
segment and cornea fellow at the Anglia University in
follows an X-linked inheritance pattern; however, females who carry the Southend-on-Sea.
defective gene can also develop variable clinical signs and symptoms
E: ines.lanzl@lrz.tu-muenchen.de
partly based on skewed X-chromosome inactivation.
11,12
The estimated
prevalence of Fabry disease is 1:40,000 males.
9
Bart P Leroy is an ophthalmologist and ophthalmic
geneticist in the Department of Ophthalmology and the
Centre for Medical Genetics at the Ghent University
Clinical Course
Hospital (GUH). His research topics include Leber congenital
In ‘classic’ Fabry disease, early symptoms typically arise in childhood or amaurosis and bestrophinopathies. Dr Leroy completed his
adolescence and generally include neuropathic pain, angiokeratoma,
training in genetics and ophthalmology at the GUH, with
further studies in ophthalmic genetics and visual
hypohidrosis, gastrointestinal disturbances, ocular manifestations and
electrophysiology at Moorfields Eye Hospital and the
exercise intolerance. Neuropathic pain is often the earliest symptom in
Institute of Ophthalmology, University College London.
affected males and females. Two types of pain are common:
© TOUCH BRIEFINGS 2008 55
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