Mucopolysaccharidoses


HURLER SYNDROME


Hurler syndrome (MPS I-H) has an autosomal recessive inheritance and is caused by a deficiency in α-L-iduronidase. Elevated amounts of dermatan and heparan sulfates are identified due to the enzyme deficiency. The severity of enzyme deficiency correlates with clinical severity.


Clinical Manifestations. Affected infants are large at birth, but growth rate decreases in the early months of life. Stature is markedly restricted, and contractures develop, limiting ambulation. Facial features progressively coarsen, and the nasal bridge flattens. Corneal clouding, hepatosplenomegaly, joint stiffness, claw-hand deformity, and thoracolumbar kyphosis develop slowly. Hernias, hirsutism, macrocephaly, macroglossia, noisy respirations, and mucoid rhi-norrhea are present by the second year of life.


Mental retardation is severe, with a lag in developmental milestones. Cardiac murmurs, deafness, and poor vision develop with time, and respiratory complica-tions become more frequent. A combination of cardiac and pulmonary problems usually causes death between 6 and 12 years of age.


Radiographic Findings. Common to all the mucopolysaccharidoses are multiple skeletal changes that vary in severity. In patients with Hurler syndrome, the J-shaped sella turcica is enlarged, the skull is scaphocephalic, and the ribs are splayed. Other major findings include beaking of the lumbar verte-bral bodies, kyphosis with gibbus formation in the thoracolumbar area, and abnormally short and broad long bones. Modeling of the metacarpals is poor, and their proximal ends are pointed. Broad, short phalanges contribute to claw-hand deformity.


Laboratory Findings. A high concentration of acid mucopolysaccharides, primarily dermatan sulfate and heparan sulfate, is found in the urine. There is a deficiency of lysosomal enzyme α-L-iduronidase in fibroblasts or leukocytes, and metachromatic granules may be observed in leukocytes.


HUNTER SYNDROME


Hunter syndrome (MPS II) is transmitted as an X-linked recessive trait. It is caused by a deficiency of the enzyme iduronate-2-sulfatase. Heparan sulfate is found to be in excess.


Clinical Manifestations. Clinical signs, present only in males, may not appear until age 2 or 3. The phenotypic presentations develop slowly. Two subtypes are recognizable. The severe form (MPS II-A) is marked by progressive mental retardation, and death occurs before age 15. A mild form (MPS II-B) is compatible with survival to adulthood and reproduction.


Affected persons are generally taller than those with Hurler syndrome, reaching a height of 47 to 59 inches. Coarse facies, joint stiffness and contractures, claw-hand deformity, hepatomegaly, hernias, cardiac complications, hirsutism, and deafness are major features. Usually, corneal clouding is not clinically evident, although in older patients, slit lamp examination may reveal a light haze. Occasionally, a pebble-like rash is seen in regions of the scapula and upper arm.


Radiographic Findings. Findings of enlarged sella turcica, spatulate ribs, beaking of lumbar vertebrae, kyphosis, and short and broad long bones are less pronounced than those in Hurler syndrome.


Laboratory Findings. Increased levels of chondroitin sulfate B and heparan sulfate are seen in the urine. The lysosomal enzyme α-iduronidase is deficient in cultured fibroblasts.


MORQUIO SYNDROME


Morquio syndrome (MPS IV) has an autosomal recessive inheritance caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfate sulfatase, which is essential for the breakdown of keratan sulfate and chondroitin-6-sulfate.


Clinical Manifestations. Appearance at birth is normal, but the growth rate is usually restricted by 2 years of age and ceases by age 12. Medical attention is sought for dwarfism, awkward gait, knock-knee, bulging sternum, flaring of the rib cage, flatfoot, prominent joints, cervical instability, or dorsal kyphosis. Corneal clouding develops between 5 and 10 years of age but is not as severe as in Hurler syndrome. The teeth are discolored and have easily fractured enamel. Ligamentous laxity can be extreme, particularly at the wrists. Severe knock-knee may interfere with ambulation.


Other complications include aortic regurgitation and atlantoaxial instability leading to spinal cord compression, which may, in turn, lead to quadriparesis. Adult height is less than in Hunter syndrome, ranging from only 32 to 47 inches.


Radiographic Findings. Flattened vertebrae with central anterior projections in the lumbar spine, odontoid aplasia or hypoplasia, delayed development of ossification centers, wide ribs, pointed proximal metacarpals, and coxa valga are the principal findings.


Laboratory Findings. The presence of keratan sulfate with normal or elevated levels of acid mucopolysaccharides in the urine is typical and is associated with a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase in cultured fibroblasts.


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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Mucopolysaccharidoses
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