EU_Musc_Manger.qxp 24/4/08 11:17 Page 22
Mucopolysaccharidosis Type I
Rheumatological Manifestations Are Key in the Early Diagnosis of
Mucopolysaccharidosis Type I
a report by
Bernhard Manger
Attending Physician, Outpatient Department of Clinical Immunology and Rheumatology, Department of Medicine III, Erlangen Medical School
Among rare diseases, usually defined as disorders with a prevalence of valvular disease was diagnosed at 35 years of age, and the patient
fewer than five cases per 10,000 in the community, there are more than underwent cardiac surgery seven years later. She also suffered from
100 rheumatic diseases.
1
Therefore, rheumatologists are accustomed to progressive hearing impairment as well as loss of vision due to retinal
recognising and assigning symptoms of these disorders. Some rare degeneration and increasing clouding and thickening of the cornea that
diseases with musculoskeletal symptoms, such as the lysosomal could not be relieved by laser-based surgery or cornea transplants. She
storage disease mucopolysaccharidosis type I (MPS I), are now treatable. progressed to partial deafness and eventually went blind. At the age of
Affected patients can now benefit from early diagnosis, which provides 52 years, when she saw a neurologist to receive treatment for vertigo, a
an opportunity for treatment before irreversible damage occurs. diagnosis of MPS I (Scheie) was finally suspected and confirmed, almost
Recognising the key symptoms of rare diseases can be a challenge. As 50 years after the first symptoms had appeared.
patients with Scheie-type MPS I may first seek medical assistance for their
musculoskeletal symptoms, awareness of these rheumatological Case Report 2
manifestations is key in the early diagnosis of the disease. In order to help This patient was diagnosed and treated in one of the specialist centres
fellow rheumatologists to recognise and identify the symptoms of MPS I, that contributed to the aforementioned survey.
2
The case has previously
two case reports will be presented and the most common been presented in a paper on rheumatological manifestations of the
musculoskeletal symptoms of the disease will be discussed in the context lysosomal storage diseases Gaucher disease, Fabry disease and MPS I.
3
of common rheumatological misdiagnoses.
Case Report 1
As patients with Scheie-type MPS I may
This case was recently described in a paper on 13 patients with the
Scheie-type attenuated form of MPS I treated at five European centres
first seek medical assistance for their
specialising in the management of lysosomal storage diseases.
2
A healthy
musculoskeletal symptoms, awareness of
Italian girl, presenting with stiffness of one finger at three years of age,
these rheumatological manifestations is
had been diagnosed as having juvenile idiopathic arthritis (JIA), resulting in
short-term treatment with steroids. At 24 years of age, bilateral equino key in the early diagnosis of the disease.
varus foot deformity was diagnosed and corneal clouding was noticed.
Seven years later, when she was referred to an orthopaedist because of a
limp, dysplasia of the femoral head and the acetabulum was diagnosed by A healthy German boy presented with a trigger finger at two years of
X-ray. The patient was also given a diagnosis of rheumatoid arthritis (RA), age. At three years of age he had increasing pain in both hands, was
although the hand deformities were not of the classic RA type, there were diagnosed with carpal tunnel syndrome and underwent surgery. While
no signs of inflammation and rheumatoid factor was negative. early flexion contractures mainly in the metacarpophalangeal (MCP) and
interphalangeal joints progressed until the boy could not close his fist,
The diagnosis of RA resulted in treatment with gold salts and the elbows and knees were not affected. Progressive shortening of the
non-steroidal anti-inflammatory drugs (NSAIDs), which did not provide Achilles tendons occurred in both feet at five years of age and resulted in
any relevant clinical benefit. Progressive cardiac dysfunction due to equinus foot deformity with chronic pain (see Figure 1). There were no
signs of an inflammatory process or autoimmune disease and the boy did
Bernhard Manger is an Associate Professor of Internal Medicine,
not benefit from treatment with NSAIDs. Corneal clouding as well as
and an Attending Physician in the Outpatient Department of moderate mitral and mild tricuspid insufficiency were noticed at nine
Clinical Immunology and Rheumatology Department of Medicine
years of age. Based on an analysis of the urinary excretion of
III, at Erlangen Medical School. He is a member of several
professional organisations, including the German Society of
glycosaminoglycans (GAGs) and a decreased activity of a-iduronidase, the
Immunology (DGfi), the American Association of Immunologists
boy was diagnosed with MPS I (Scheie-type) and began enzyme
(AAI) and the German Society for Rheumatology. He is a
reviewer for many respected journals, including the American
replacement therapy.
Journal of Medicine, Arthritis and Rheumatism and the Journal of
Rheumatology. Dr Manger received his medical degree from Erlangen Medical School, and trained
Mucopolysaccharidosis Type I – The Clinical Picture
in internal medicine and rheumatology at the Erlangen Medical School and the Department of
Clinical Immunology and Rheumatology at the University of California, San Francisco.
MPS I is a complex, progressive disease affecting multiple organs. The
recessively inherited genetic defect results in deficient activity of
E:
bernhard.manger@uk-erllangen.de
a-L-iduronidase, a lysosomal hydrolase that catalyses the hydrolysis
of terminal a-L-iduronic residues of dermatan sulfate and heparan
22 © TOUCH BRIEFINGS 2008
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