Alpha-Mannosidosis

Characterized by Hurler-like facial features, moderate-to-severe mental retardation, recurrent pulmonary infections, reduced hearing, immunodeficiency, skeletal abnormalities, and primary central nervous system disease, mainly ataxia. It is also frequently associated with corneal opacities, aseptic destructive arthritis, and metabolic myopathy. Communicating hydrocephalus can occur in individuals of any age. Cardiac and renal complications are rarely encountered. Alpha-mannosidosis is insidiously progressive. Individuals may live into the sixth decade.

Lysosomal Alpha-D-mannosidase Deficiency; Alpha-Mannosidase B Deficiency; Mannosidosis.

Very little is known about the prevalence of alpha-mannosidosis. A study from Australia reported prevalence of one in 500,000. A study from Norway reported six individuals in a population of four million. The disease is not specific to any ethnic group, as individuals from all parts of the world have been described.

It is inherited as an autosomal recessive trait.

There are three types of alpha-mannosidosis that be suggested:

Type I (Mild Juvenile)

Mild form delineated by clinical recognition of the disease after age ten years, with absence of skeletal abnormalities, myopathy, and slow progression.

Type II (Mild Infantile)

Moderate form with clinical recognition before age ten years, with presence of skeletal abnormalities, myopathy, and slow progression.

Type III (Severe Infantile)

Severe form with obvious progression, leading to early death from primary central nervous system involvement or infection.

Alpha-mannosidosis is one of a group of very rare inherited disorders known as glycoprotein and related storage diseases. These disorders are caused by a defect in the breakdown of complex molecules in the cells, as a result of an enzyme deficiency. The enzyme that is lacking is known as alpha-D-mannosidase. The molecules that are not broken down are stored in the small components within cells known as lysosomes.

The diagnosis relies on demonstration of deficient acid alpha-mannosidase enzyme activity in peripheral blood leukocytes or other nucleated cells such as fibroblasts, amniocytes, or the trophoblast. The diagnosis can be confirmed by measuring the presence of urinary oligosaccharides. Alpha-mannosidase is needed for the catabolism of many oligosaccharides and glycoproteins.

Infiltration of tissues with oligosaccharides and glycoproteins results in vomiting, hepatosplenomegaly, large head, thick calvaria, low anterior hairline, coarse facial features (Hurler-like), thick eyebrows, flat nose, large ears, macroglossia, widely spaced teeth, gingival hypertrophy deafness, lens opacities, prognathism, tall stature, ataxia, and muscular hypotonia. Other clinical features include lumbar gibbus, big hands and feet, dysostosis multiplex, bowed femurs, storage cells in bone marrow, vacuolated lymphocytes, pancytopenia, recurrent respiratory tract infections, immunoglobulin deficiency, hypogammaglobulinemia, antiplatelet antibodies, antineutrophil antibodies, low haptoglobin level, and severe mental retardation (adult form). Pectus carinatum, skeletal abnormalities, dilated cerebral ventricles and raised intracranial pressure, spondylolysis and spondylolisthesis of L5 on S1.

Upper airway obstruction is a major consideration in these patients. The airway management will be comparable to patient affected with Hurler syndrome. A potentially difficult airway management, including direct laryngoscopy and tracheal intubation must be anticipated and proper equipment prepared. Spontaneous respiration must be maintained until confirmation that ventilation can be ensured with face-mask ventilation or when confirmation of lung ventilation after tracheal intubation. The use of awake fiberoptic intubation with or without a laryngeal mask airway is highly recommended. Obtain cell blood count and differential, a 12-lead ECG, chest x-ray, and 2D echocardiography in all patients when possible. The pulmonary system must be assessed carefully for the presence of restrictive and/or reactive airway disease. Obtain an arterial blood gas determination and pulmonary function tests when the patient is cooperative. The use of preoperative bronchodilator therapy must be considered. Patients may be uncooperative depending on level of mental retardation, making induction of anesthesia difficult. The use of preoperative sedation and/or anxiolytic is not advisable in severely affected patients. Each patient must be evaluated individually before sedation is given. Centroneuraxial regional anesthesia is relatively contraindicated in patients with moderate to severe spinal deformities. Attainment of intravenous access may be difficult. Patients may experience bleeding disorders with the presence of antiplatelet antibodies. Obtain coagulation studies preoperatively.

There are approximately 50 diseases known as lysosomal storage diseases. In addition to alpha mannosidosis and a related disorder, beta mannosidosis, the lysosomal storage disorders include Fabry disease, Gaucher disease, cystinosis, aspartyl glycosaminuria, mucopolysaccharidoses, mucolipidoses, and many others.