Lanzl_edit.qxp 24/9/08 12:54 Page 57
Ocular Features of Treatable Lysosomal Storage Disorders
variety of cell types, stabilisation of kidney function in patients with
Figure 4a: Flexion Contractures of the Fingers of a
relatively preserved kidney function and reduction of the probability of a
Mucopolysaccharidosis I Patient
major clinical event may be anticipated. Responses of ophthalmological
pathology to ERT have not yet been studied in formal clinical trials.
Mucopolysaccharidosis I (Hurler, Hurler-Scheie and
Scheie Disease)
MPS I is an autosomal recessive inborn error of metabolism caused by
mutations in both alleles of the gene encoding the lysosomal enzyme
α-L-iduronidase.
30
It represents the most common disorder of the group
of seven MPS, with an estimated prevalence of 1:100,000 newborns. The
enzyme deficiency leads to the inability of lysosomes to break down the
glycosaminoglycans (GAGs) dermatan sulphate and heparan sulphate,
which are important components of the extracellular matrix surrounding
cells and integral parts of the cell membranes. They play a major role in
the structure of the cornea, connective tissue and cartilage, as well as in
joint fluids, and their metabolic degradation is essential for normal
growth and tissue homeostasis. Progressive accumulation of undegraded
GAG occurs in virtually all tissues and gradually causes tissue and organ
Figure 4b: Female Scheie Patient with Typical Coarse Facial
dysfunction, with eventual cellular death throughout the body.
30–32
Features and Deformation of Joints
Clinical Course
The wide spectrum of clinical disease spans from the most severe form
(Hurler disease) to less aggressive forms of the disease (the Hurler-Scheie
and Scheie phenotypes).
31–33
In Hurler patients, the disease progresses
rapidly. Patients are commonly diagnosed at around the age of nine
months and cognitive defects and developmental delay usually become
apparent before the age of two years. Patients will be severely mentally
retarded and have pronounced somatic disease manifestations at the
time of early demise, often before the age of 10 years. In more
attenuated cases, joint pain and stiffness with difficulty in using the
hands (see Figure 4a), corneal clouding, ear–nose–throat infections and
recurrent umbilical hernia generally manifest before the age of two years.
Coarse facial features, hepatomegaly, hearing difficulties and delayed
speech development are common. Life expectancy in attenuated forms
may be limited to <20 years, whereas Scheie patients with fewer physical
symptoms may survive well into adulthood (see Figure 4b). However,
Figure 5: Scheie Patient after Corneal Transplant
cardiac insufficiency or complications of, for example, spinal surgery may
reduce life span if cause-specific treatment and adequate supportive care
are not administered.
Ocular Features
The main ocular manifestations of MPS I include corneal clouding, retinal
pigmentary degeneration, glaucoma and optic nerve abnormalities.
6
Prominent, wide-set eyes (shallow orbits, hypertelorism) may be seen in
severely affected patients.
Cornea
Corneal opacities are universally present in all forms of MPS I.
31
Fine grey
punctate opacities are first seen in the anterior stroma; later, as the disease
progresses, they are also seen in the posterior stroma. Progressive corneal
opacification is typically diffuse and is associated with photosensitivity and
reduced central visual acuity. There are reports of denser clouding in the
peripheral cornea in MPS disease with good visual acuity as a result of
Note the opacities in the recipient cornea and clear donor cornea.
minimal central corneal involvement, especially in attenuated cases.
34
Corneal grafts may improve visual acuity in such cases (see Figure 5). In ophthalmologist considers a possible diagnosis of MPS I, particularly in the
severe cases, vision is impaired in early childhood and nystagmus may be presence of other suspect clinical symptoms. However, other diseases
present. If corneal clouding is detected it is important that the should also be considered in the differential diagnosis (see Table 1).
EUROPEAN OPHTHALMIC REVIEW 57
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100