MORQUIO SYNDROME C

MORQUIO SYNDROME C Alternative titles; symbols MORQUIO SYNDROME, NONKERATOSULFATE-EXCRETING TYPE Clinical Synopsis TEXT Description Morquio syndrome is an autosomal recessive mucopolysaccharidosis characterized by short trunk dwarfism, fine corneal opacities, skeletal changes, and normal intelligence. Morquio syndromes A (MPS4A; 253000) and B (MPS4B; 253010) are caused by mutations in the N-acetylglucosamine-6-sulfate sulfatase (GALNS; 612222) and beta-galactosidase (GLB1; 611458) genes, respectively. MPS4A and MPS4B are characterized biochemically by increased urinary excretion of keratan sulfate (Beck et al., 1986). There is some evidence of an additional form of Morquio syndrome, referred to here as type C, in which urinary excretion of keratan sulfate is absent. However, McKusick (1972) suggested that the nonkeratosulfate- excreting Morquio syndrome may be allelic to other forms of Morquio syndrome. Clinical Features McKusick (1972) described a girl with a mild form of Morquio disease and absence of urinary keratosulfate excretion. She presented at age 6 years with increased anteroposterior chest diameter, genu valgum, and enlarged knees and knuckles (see McKusick, 1960, p. 271, fig. 91). Radiographs at age 10 years showed platyspondyly and changes in the femoral heads. She later married and delivered a healthy boy by cesarean section. Examination as an adult showed short-trunk dwarfism, hyperextensible wrists, and mild corneal opacities, none of which were as severe as seen in classic Morquio disease. She had 3 cousins who were similarly affected. The disorder in this family was atypical because of the milder skeletal and extraskeletal features and the lack of mucopolysacchariduria. These patients belonged to a consanguineous kindred of Early Americans in southern Maryland in which several autosomal recessive disorders, including Crigler-Najjar syndrome (218800), had been observed. McKusick (1972)suggested that the condition in this family represented a 'nonkeratansulfate-excreting' form of Morquio syndrome, which he postulated was likely allelic to other forms of Morquio syndrome. In addition, he suggested that it may be possible that these patients are in fact 'keratansulfate excretors,' but that the keratansulfaturia which progressively diminishes with age in all Morquio cases decreased more quickly in these patients. Maroteaux et al. (1982) described 2 children, aged 8 and 7 years, who had a mild form of Morquio syndrome and absence of urinary keratosulfate excretion. Clinical features included characteristic short trunk dwarfism and discrete corneal opacities apparent on slit-lamp examination. Radiographic studies showed moderate platyspondyly and hypoplasia of the odontoid process. Epiphyseal cartilage chondrocytes were large and contained numerous vacuoles limited by a single smooth membrane, as in classic Morquio syndrome. However, the activities of N-acetylgalactosamine-6-sulfate sulfatase and beta-galactosidase were normal. Beck et al. (1986) suggested that this disorder may represent a 'type C' Morquio syndrome. Fujimoto and Horwitz (1983) studied 2 offspring of second-cousin Mexican parents described as having 'nonkeratosulfate-excreting Morquio syndrome.' The proband presented at age 13 years with pes planus. He was at the third percentile for height and had a broad, prominent chest, soft systolic murmur, dysplastic hips, and fine corneal deposits. Radiographs showed abnormal vertebrae without kyphosis or scoliosis. The odontoid process appeared normal. His younger sister had a broad chest and platyspondyly with tongue-like protrusions of anterior portions of the lumbar spine. Although there was no urinary keratan sulfate, both patients had high levels of urinary chondroitin-6-sulfate. Multiple assays on N-acetylgalactosamine-6-sulfatase in leukocytes and cultured skin fibroblasts showed deficiency of this enzyme in the range found in classic Morquio A syndrome. Fujimoto and Horwitz (1983) postulated that the patients had a mild variant of Morquio A. Beck et al. (1986) reported a 30-year-old man who was 156 cm tall and had severe hip disease, fine corneal deposits by slit-lamp, and a wedge-shaped first lumbar vertebra. There was no increase in urinary keratan sulfate or chondroitin sulfate. However, GALNS activity was markedly decreased in fibroblasts, suggesting a variant of Morquio A. See Also: Norman (1974) REFERENCES 1. Beck, M., Glossl, J., Grubisic, A., Spranger, J. Heterogeneity of Morquio disease. Clin. Genet. 29: 325-331, 1986. [PubMed: 3087664, related citations] [Full Text: Pubget] 2. Fujimoto, A., Horwitz, A. L. Biochemical defect of non-keratan-sulfate-excreting Morquio syndrome.Am. J. Med. Genet. 15: 265-273, 1983. [PubMed: 6224421, related citations] [Full Text: Pubget] 3. Maroteaux, P., Stanescu, V., Stanescu, R., Kresse, H., Hors-Cayla, M. C. Heterogeneite des formes frustes de la maladie de Morquio. Arch. Franc. Pediat. 39: 761-765, 1982. [PubMed: 6219649, related citations] [Full Text: Pubget] 4. McKusick, V. A. Heritable Disorders of Connective Tissue. St. Louis: C. V. Mosby (pub.) (4th ed.) : 1972. 5. McKusick, V. A. Heritable Disorders of Connective Tissue. St. Louis: C. V. Mosby (pub.) (2nd ed.) : 1960. 6. Norman, M. E. Two brothers with nonkeratan-sulfate-excreting Morquio syndrome.In: Bergsma, D. : Skeletal Dysplasias. Amsterdam: Excerpta Medica (pub.) 1974. Pp. 467-469.