Hurler Syndrome, Hurler-Scheie Syndrome, and Scheie Syndrome (Mucopolysaccharidosis Type I) Clinical Presentation

Updated: Sep 28, 2018
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Presentation

History

Historically, the most-to-least severe subtypes of MPS I were as follows: Hurler syndrome (MPS IH, OMIM #607014), Hurler-Scheie syndrome (MPS I-HS, OMIM #607015), and Scheie syndrome (MPS IS, OMIM #6076016). These classifications are arbitrary categorizations of points on a spectrum of patient phenotypes and represent clinical phenotypes ranging from most severe to least severe.

Currently, no biochemical differences between these subtypes have been identified, and their clinical findings overlap. MPS I is now divided into two subtypes; (1) severe MPS I (Hurler syndrome) and (2) attenuated MPS I (Hurler-Scheie syndrome and Scheie syndrome).

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Physical

Clinical manifestations of mucopolysaccharidosis type I (MPS I) show a chronic multisystemic and progressive course. [3] The disease is highly heterogeneous, spanning a spectrum of severity.

Individuals with Hurler syndrome, considered the severe end of the syndrome spectrum, appear normal at birth and develop the characteristic phenotype over the first years of life.

Phenotypic features seen in both MPS I and attenuated MPS I include facial dysmorphism, corneal clouding, hepatomegaly, valvular heart disease, obstructive airway disease, [4] developmental delay, hearing loss, skeletal deformities, [5] and joint stiffness.

In individuals with severe disease, symptoms arise early in life. These include multisystemic progressive debilitating symptoms and include neurological impairment. They have a shortened lifespan to less than 10 years. Individuals with less-severe attenuated disease have similar phenotypic features but generally have normal intellect and stature and a normal lifespan.

The Hurler syndrome (MPS IH) clinical spectrum is outlined below. These characteristic features in children with the severe form of MPS I are less obvious in children diagnosed with attenuated MPS I.

Facial dysmorphism or coarsened facial features

Coarse facial features become apparent at age 3-6 months and may progress with age.

The individual’s head is large (macrocephalic) with frontal bossing. The skull shape is often scaphocephalic owing to premature closure of the metopic and sagittal sutures. The individual’s eyes may be wide-spaced (hypertelorism) with shallow eye sockets, causing the eyes to protrude slightly. Depressed nasal bridge with broad nasal tip and anteverted nostrils is seen. Chronic nasal discharge is present. Lips are enlarged. Oropharyngeal features include a high-arched palate with macroglossia. Mandibular prognathism is present.

The clinical presentation of attenuated MPS I may be limited to mildly coarse facial features and mandibular prognathism.

Corneal clouding

As a result of glycosaminoglycan (GAG) storage and accumulation, progressive corneal clouding is common in MPS I and can begin within the first year of life. Corneal clouding has a ground-glass appearance and can lead to blindness. Retinal degeneration is also common in MPS I.

Visceral involvement

Progressive hepatosplenomegaly is common in MPS I. GAG storage in the liver and spleen does not lead to organ dysfunction; however, organ size may be markedly enlarged. Loose stools and diarrhea are episodic problems for some patients. Inguinal and umbilical hernias are common. They are occasionally present at birth or develop within the first several months of life and are often one of the first clinical signs noted.

Skeletal involvement

Patients with severe disease demonstrate skeletal manifestations of MPS I early in life, by about age 6 months. At that time, widening of the ribs and mild bone abnormalities (detected by radiological methods) are common, particularly within the hip and ovoid vertebrae. At the clinical level, skeletal involvement does not become obvious until age 10-14 months, when a gibbus deformity of the back, or dorsolumbar kyphosis, is observed in patients with severe disease.

Eventually, progressive skeletal dysplasia involving all bones is seen in all types of MPS. The vertebrae may become progressively flattened and beaked, often leading to spinal deformity. Typically, the pelvis is poorly formed, with small femoral heads and coxa valga. Involvement of the femoral head leads to progressive and debilitating hip deformity. Clavicles may be short, thickened, and irregular (“oar-shaped”).

Height progresses normally until about age 2 years; subsequently, linear growth stops. By age 3 years, height is less than the third percentile. Patients may not reach an overall height of greater than 4 feet.

Joint stiffness

The joints may become stiffened by age 2 years, and progressive arthropathy affects all joints. The hands take on a characteristic "claw" deformity, resulting from both phalangeal dysostosis and synovial thickening.

Carpal tunnel syndrome, a common complication in the MPSs, probably results from a combination of excessive lysosomal storage in the connective tissue of the flexor retinaculum and a deformity secondary to the underlying skeletal dysplasia.

Cardiopulmonary

Valvular disease, specifically aortic valve disease, may be seen in these patients. Frequent upper and lower respiratory tract infections are common. Respiratory obstruction results from enlargement of tonsils, adenoids, and tongue.

Development

In severe forms of MPS I, developmental delay is often apparent by age 12-24 months, reaching a maximum functional age of 2-4 years, followed by progressive deterioration. Language skills are often limited and can be related to hearing impairment due to chronic hearing loss/deafness. In mild forms, intellect may be within a normal range.

Others

The neck is short, and odontoid hypoplasia is noted. Vertebral subluxation with cord compression can occur. Hirsutism is present, and body hair may be coarser than usual.

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Causes

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the lysosomal enzyme, alpha-L-iduronidase. [6] This deficiency leads to accumulation of undegraded mucopolysaccharides, especially dermatan sulfate (DS), in tissues and organs. The buildup of excess dermatan sulfate leads to the gradual development of numerous morphological abnormalities in tissues and organs. The alpha-L-iduronidase gene has been mapped to the short arm of chromosome 4, band 16.3 (4p16.3). MPS I is inherited as autosomal recessive.

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