Alpha-mannosidosis is a rare inherited lysosomal storage disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. Alpha-mannosidosis is divided into three subtypes: a mild, slowly progressive form (type 1); a moderate form (type 2); and a severe, often rapidly progressive and potentially life-threatening form (type 3). Symptoms range widely in their onset and severity. Symptoms may include distinctive facial features, skeletal abnormalities such as osteopenia, calvaria, vertebrae, bowed legs or knock knees, and deterioration of the bones and joints, hearing loss, intellectual disability, and dysfunction of the immune system, such as lupus erythemadoses, pancytopenia, hypothyroidism or primary biliary cirrhosis. Prevalence is estimated to be 1 in 500,000 live births.
Diagnosis of the condition is based on measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells, and it can be confirmed by genetic testing for the MAN2B1 gene. Management should be proactive, preventing complications and optimizing quality of life, and may include early use of antibiotics for bacterial infections, hearing aids for hearing loss, insertion of pressure-equalizing tubes if fluid accumulates in the middle ear, glasses to correct refractive error, physiotherapy, use of a wheelchair, orthopedic intervention, and shunting as needed for hydrocephalus. Educational considerations may include use of sign language for individuals with hearing loss, early educational intervention for development of social skills, speech therapy, and special education to maximize learning.
Bach et al. (1978) reported two sibs, born of consanguineous Palestinian parents, with mild mental retardation, delayed speech, coarse facies, and limited mobility of the large joints. Cultured fibroblasts showed partial alpha-mannosidase deficiency (20% of normal), and the sibs were considered to be mildly affected. However, both patients had vacuolated leukocytes and fibroblasts consistent with the disease phenotype. Nilssen et al. (1997) studied these two sibs and identified a homozygous mutation in the MAN2B1 gene.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Lysosomal storage disorders were the most diagnosed category of IEM in this cohort (74 out of 248 cases, 30%). Among them, 2 cases from a single family were found to have mannosidosis with an estimated incidence of 1 per 100,000 live births. All cases of lysosomal storage disorders were confirmed through enzymatic assays on skin fibroblasts, liver biopsy or leukocytes. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Al-Jasmi et al. (2013) studied the prevalence of lysosomal storage diseases (LSDs) in the UAE and reported their mutation spectrum. This study included all the patients diagnosed and followed up between 1995 and 2010 at the only two metabolic referral centers in the country. In this period, a total of 119 patients, 65 of them Emiratis, were diagnosed with LSDs. Six patients with Batten disease were identified in this study; five of them Emiratis, giving a high birth prevalence of 1.51 per 100,000 for Emiratis. Of these five patients, three belonged to one tribe, while the remaining two were from one other tribe. Phenotypically, the patients from the first tribe showed severe mental retardation and hearing loss, while the affected patients in the second tribe had mild mental retardation, were diagnosed early, and required a bone marrow transplantation.