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Idiopathic Osteonecrosis of Femur in Adult Morquio Type B Disease To the Editor: Morquio syndrome is one of the mucopolysaccharidoses (type IV). Glycosaminoglycans accumulate within the cells, leading to many systemic alterations and skeletal abnormalities. There is shortening of the trunk and limbs, spinal curvature, odontoid hypoplasia with cervical instability, and lower-limb alignment problems1. We describe a young man originally diagnosed with idiopathic osteonecrosis of femur. A male patient born in 1975 had dystonia since he was 11 years of age. It was first localized to the upper limbs, but progressively generalized, with an axial predominance, when he reached age 20 years. The dystonia caused walking difficulties, but he had no mental problems and he worked normally in a computer business. No dysmorphic features (height 1.69 m, weight 57 kg) or visceral or other neurological abnormalities were found, cerebral magnetic resonance imaging examination was normal, and the dystonia was considered idiopathic. At age 23 years, he suddenly complained of a pain in the right hip, when walking. On the pelvic radiograph there was a typical aspect of osteonecrosis of the right femoral head with a normal left hip and absence of dysplasia on both sides (Figure 1A, 1B). Radiographs of other joints (knees, shoulders, hands, wrists, ankles, feet) were normal, and the necrosis was thought to be probably idiopathic. Comorbidities known to be associated with osteonecrosis were ruled out. Surgery was not considered, as the hip lesion did not affect his quality of life.
After 4 years of regular followup, he mentioned that a recently born niece presented a progressive psychomotor retardation, and the possibility of a genetic disorder of mucopolysaccharide metabolism was suspected. His ophthalmologic examination was normal, but spine radiographs revealed vertebral dysplasia at the cervical, dorsal, and lumbar level. There was moderate dorsal scoliosis, and at the dorsal and lumbar level platyspondyly, mild anterior tonguing, concavity of the vertebral bodies, and irregular endplates. The craniocervical junction was normal, but C5 was pear-shaped, centering a cervical kyphosis, with platyspondyly of the adjacent vertebrae (Figure 2).
Blood samples and a skin biopsy for fibroblast culture were sent to the Laboratoire de Génétique et pathologie métabolique at Hopital Cochin, Paris (Prof. L. Poenaru, Dr. C. Caillaud), and the Laboratoire de Génétique, Hopital Necker-Enfants malades (Dr. D. Geneviève), Paris. Screening for enzyme deficiency showed a very low level of leukocyte ß-galactosidase (15 nmol/h/mg proteins) representing 7.5% of the low normal range (200–700). The skin fibroblast culture confirmed the deficient ß-galactosidase activity (4 nmol/h/mg protein instead of 617 nmol/h/mg). At age 30 years, the pain at walking had increased but was still acceptable, and the appearance of the right hip remained stable. The clinical problem was then dominated by the dystonia, which was resistant to treatment. The dystonia involved the entire body but was predominantly axial. In September 2006 a pallidal deep-brain stimulation was carried out (Prof. A.L. Benabid, Prof. P. Pollak) and after this, his walking improved significantly. A diagnosis of Morquio B was determined. The usual form of Morquio disease is known as Morquio A2,3. There is stunted growth, spondyloepiphyseal dysplasia, and frequently a craniocervical junction malformation requiring a surgical fixation4. The ß-galactosidase is normal, but a-galactose 6-sulfatase is undetectable. Morquio B disease is much rarer, and tends to be less severe. Lysosomal storage disorder is caused by ß-galactosidase deficiency due to mutations in the GLB1 gene. Three major forms have been established on the basis of age of onset and severity of symptoms: infantile, juvenile, and adult5. The adult form is characterized, as in our patient, by a progressive and generalized dystonia with speech and gait disturbance and slowly progressing dementia2,3. The physiopathology of femoral head osteonecrosis is still controversial. In most cases there is a conjunction of local blood flow reduction and increased fragility of bone6. Femoral head collapse is often seen — in Gaucher disease — due to an accumulation of Gaucher cells in bone marrow7. In most of the other inherited metabolic diseases there is a joint dysplasia with more or less destruction of bone extremities3, but isolated femoral head osteonecrosis is quite rare. A few cases have been reported in Fabry's disease8. A case of Morquio disease was diagnosed as Perthes disease for 38 years9, and a mild form of Morquio A disease with bilateral Perthes disease was recognized only when the patient reached adulthood10. The association of Morquio B disease with femoral head necrosis may be coincidental, although no other risk factors were found in our patient. The accumulation of undegraded substrate in lysosomes of the affected tissues, such as bone marrow, chondrocytes, and osteocytes, may induce bone fragility, with microfractures responsible for the osteonecrosis. CHARLES J. MENKÈS, MD, Professor Emeritus; PIERRE RONDOT, MD, Université René Descartes, Paris V, Department of Rheumatology, Hospital Cochin, 95 rue de Passy, 75016 Paris, France. Address reprint requests to Prof. Menkès. E-mail: charles.menkes@wanadoo.fr 2. Muthane U, Chickabasaviah Y, Kaneski C, et al. Clinical features of adult GM1 gangliosidosis: report of three Indian patients and review of 40 cases. Mov Disord 2004;19:1334-41. [MEDLINE] 3. van Gemund JJ, Giesberts MA, Eerdmans RF, Blom W, Kleijer WJ. Morquio-B disease, spondyloepiphyseal dysplasia associated with acid beta-galactosidase deficiency. Report of three cases in one family. Hum Genet 1983;64:50-4. [MEDLINE] 4. Chirossel JP, Passagia JG, Gay E, Palombi O. Management of craniocervical junction dilocation. Childs Nerv Syst 2000; 16:697-701. [MEDLINE] 5. Santamaria R, Chabas A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio-B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat 2006;27:1060. [MEDLINE] 6. Jones LC, Hungerford DS. Osteonecrosis: etiology, diagnosis and treatment. Curr Opin Rheumatol 2004;16:443-9. [MEDLINE] 7. Katz K, Horev G, Grunebaum M, Yosipovitch Z. The natural history of osteonecrosis of the femoral head in children and adolescents who have Gaucher disease. J Bone Joint Surg Am 1996;78:14-9. [MEDLINE] 8. Lien YH, Lai LW. Bilateral femoral head and distal tibial osteonecrosis in a patient with Fabry disease. Am J Orthop 2005;34:192-4. [MEDLINE] 9. Fang-Kircher SG, Bock A, Fertschak W, Schwagerl W, Paschke E. Morquio disease in a patient diagnosed as having Perthes disease for 38 years. J Inherit Metab Dis 1995;18:94-5. [MEDLINE] 10. Kanazawa T, Yasunaga Y, Ikuta Y, Harada A, Kusaka O, Sukegawa K. Femoral head dysplasia in Morquio disease type A: bilateral varus osteotomy of the femur. Acta Orthop Scand 2001;72:18-1. [MEDLINE]
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