History
Developmental delay and growth failure are common presentations of I-cell disease. Psychomotor deterioration is rapid and progressive. Some physical signs, such as hip dislocations, inguinal hernias, hepatomegaly, joint limitation, and skin changes, may be present at birth. Coarse facial features and skeletal abnormalities become more conspicuous with time. The full clinical picture is usually evident by the first year of life.
Growth failure and failure to thrive are rapidly progressive. Birth weight and length may be decreased. Linear growth decelerates during the first year of life and ceases by age 2 years. Head circumference is usually preserved.
Developmental delay is severe and is often the presenting symptom. Infants smile and follow and grasp objects but are unable to roll over or support their weight with their legs. Generalized hypotonia and poor head control are observed. Motor delay is usually more severe than cognitive delay. The severity of developmental delay widely varies.
Coarse facial features: The characteristic facies is similar to that observed in Hurler syndrome. Gingival hypertrophy is a distinguishing feature.
Radiographic findings are as follows [8, 9] :
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Findings are similar to those observed in Hurler syndrome, a condition with which I-cell disease may be confused.
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In early infancy, periosteal new-bone formation leads to cloaking of the long bones.
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The tubular bones of the upper extremities are short and widened, and the phalanges are bullet-shaped.
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Anterior beaking and wedging of the vertebrae occur. This results in a lumbar gibbus deformity and kyphoscoliosis.
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Widening of the ribs is observed.
Frequent upper respiratory tract infections: These patients experience recurrent bouts of pneumonia, bronchitis, and otitis media.
Physical
Physical findings include the following:
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Coarse facial features
High, narrow forehead
Puffy eyelids, epicanthal folds
Flat nasal bridge, anteverted nares
Long philtrum
Prominent gingival hyperplasia and macroglossia
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Musculoskeletal abnormalities
Congenital hip dislocation
Joint stiffness and claw hand deformities
Lumbar gibbus deformity and kyphoscoliosis
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Abdomen
Umbilical and inguinal hernias
Diastasis recti
Mild hepatomegaly
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Cardiovascular findings: Aortic insufficiency murmur may be present
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Ophthalmologic findings: Corneas may be clear or hazy.
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Neurologic findings: Generalized hypotonia may be observed.
Causes
I-cell disease is an autosomal-recessive disorder caused by a deficiency of the enzyme UDP-N -acetylglucosamine: N -acetylglucosaminyl-1-phosphotransferase. Deficiency of this phosphotransferase prevents the addition of the mannose-6-phosphate recognition marker because the lysosomal enzymes are modified in the Golgi apparatus before being transported to the lysosome; therefore, lysosomal enzymes cannot be endocytosed into the lysosome for normal processing and use. [10]
The UDP-N -acetylglucosamine: N -acetylglucosaminyl-1-phosphotransferase enzyme is the product of the GNPTA gene, which has been mapped to chromosome band 4q21-q23. Various mutations in this gene have been reported in patients with I-cell disease. [11]
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Profile view of 3-year-old with I-cell disease. Growth ceased more than one year earlier. Note small orbits, proptotic eyes, full and prominent mouth caused by gingival hypertrophy, short and broad hands, stiffening of small hand joints, prominent abdomen with umbilical hernia, and limited extension of the hips and knees.
