Hurler Syndrome

Also called Gargoylism or Mucopolysaccharidosis I-H, this condition was first described by Hurler. It was given name of Gargoylism by Ellis, Shelton and Capon since the condition is characterized by dwarfism with a heavy ugly facial appearance, corneal opacities, mental deficiency and enlargement of the liver and spleen.

The condition is familial ( exists in families) and genetic transmission is as an autosomal recessive.

The condition is usually first noted during early childhood though the facial appearance may be noted soon after birth. It is a rare abnormality. There is urinary excretion of dermatan sulphate and heparin sulphate and cytoplasmic metachromasia in fibroblasts derived from skin culture.

Clinical Features

The head is large, the eyes set wide apart with prominent supra-orbital ridges and coarse dark eyebrows, the bridge of the nose is depressed and there is often a chronic rhinitis.

The mandible is large and the tongue thick, the teeth are widely separated and poorly formed, the neck is short and the ears are set low on the head. The abdomen is protuberant because of an enlarged liver and spleen and there may be umbilical and inguinal herniae.

The spine develops thoracolumbar kyphosis and is short. The hands are short and thick and the fingers are stubby, with stiff flexed interphalangeal joints. The whole body surface is covered by fine hair.

Mental deficiency is usually present with retardation of sitting, standing, talking and walking. Hydrocephalus develops in some case because of meningeal deposits.

At some time between the first and third year, the cornea begins to show clouding, due to the presence of multiple opacities in the deeper layers of the cornea, and this leads to progressive loss of sight. There may be other abnormalities such as congenital glaucoma and retinal degeneration.

Audiometry often reveals the existence of deafness.

The major joints show limitation of movement and deformities develop in flexion at the hips and knees with deformities like coxa valga, genu valgum and pes planovalgus.

Paraplegia may develop because of narrowing of the spinal canal in the region of the thoracolumbar kyphosis, or quadriplegia by similar narrowing in the cervical spine.

Radiological Appearances

In the very young infant, radiological recognition is difficult, though an anterior hypoplasia of one lumbar vertebra can be recognized in early life. Towards the second year of life, generalized changes become evident.

The main changes are in the skull, spine, hip joints and upper limb bones.

The cranial vault is enlarged.Its bones are thick and dense. The sella turcica is elongated, shallow and shaped like a shoe. The optic foramina are large.

The spine shows an angular kyphosis, one of the vertebral bodies being smaller than the others and displaced backwards. Similar changes with localized kyphosis, may occur in the cervical spine.

The upper and lower surfaces of the vertebral bodies are convex, the intervertebral discs being biconcave and the most affected vertebral bodies have an anterior beak projecting from the lower part of the front of the body. This shape is produced by protrusion of the nucleus pulposus causing compression atrophy of the anterosuperior portion of the vertebral body.

The ribs are wide and splayed anteriorly like a canoe paddle.

The radius and ulna are characteristically short and thick and taper distally with the inward tilting of the distal radioulnar epiphysial line. The metacarpals are narrow proximally and the pahalnges are short and broad with hypoplasic terminal phalanges.

The lower limb bones are less affected.

There is valgus of the femoral necks and the acetabula are shollow and the acetabular roofs oblique. The pelvic inlet is narrowed with an hourglass appearance. The lower femoral and upper tibial epiphyses show some irregular with valgus deformity.

Pathology

Globules of mucopolysaccharide are found in liver cells, spleen and lymph nodes. The meninges are thickened and the nervous system contains deposits of monosialo-gangliosides. The growth cartilage shows some disorganization of the cell columns and irregularity in the maturation zone. Deposits of orange material occur on the heart valves and in the intima of the coronary vessels.

Collagen fibres are swollen and lack normal fibrillary characteristic. Electron microscopy studies show abnormal vesicles containing mucopolysaccharide. Chondrocytes and osteocytes show enlargement and vacuolization.

Differential Diagnosis

• Sondyloepiphisial dysplasias
• Other mucopolysaccharidoses
• Similar mucolipidoses.

In Hurler’s disease, the presence of mental retardation, liver from spleen enlargement and corneal opacities are characteristic.

Detection of the disease

Analysis of acid mucopolysaccharide excretion in the urine shows s marked increase in dermatan sulphate with a slight increase in heparin sulphate, which aids differentiation from other mucopolysaccharidoses does and from similar conditions without mucopolysacchariduria.

Skin fibroblasts cultured from patients and heterozygous carriers contain metachromatic granules with an increased uronic acid content.

The defect in these fibroblasts may be corrected if fibroblasts from Hunter’s syndrome or from normal persons are mixed with them, the correcting factor being the enqyme alpha-L-iduronidase.

These tests can also be applied to fluid obtained by amniocentesis to allow diagnosis before birth. Culture of cells from either parent may allow diagnosis of Hunter’s syndrome, which is sex-linked, from Hurler’s syndrome. If the disease is sex-linked and recessive, the father’s culture shows no metachromasia, but it autosomal recessive, as in Hurler’s syndrome, metachromasia is present.

Prognosis and Treatment

Many children with Hurler’s disease die in childhood.

If they survive, the extensive skeletal deformities, mental deficiency and blindness make them helpless and crippled.

Osteotomy may occasionally be needed to diminish deformity that prevents sitting or makes nursing difficult.