alpha-mannosidosis

Alpha-mannosidosis is a lysosomal storage disorder, first described by Swedish physician Okerman in 1967. In humans it is known to be caused by an autosomal recessive genetic mutation in the gene MAN2B1, located on chromosome 19, affecting the production of the enzyme alpha-D-mannosidase, resulting in its deficiency. Consequently, if both parents are carriers, there will be a 25% chance with each pregnancy that the defective gene from both parents will be inherited, and the child will develop the disease. There is a two in three chance that unaffected siblings will be carriers (Figure 1). In livestock alpha-mannosidosis is caused by chronic poisoning with swainsonine from locoweed.

==Symptoms and signs== thumb|Facial features in alpha-mannosidosis. A. Twins aged 18 Months. Note enlarged head, short neck, rounded eyebrows, saddle nose, and prominent forehead. B. Same twins aged 8 years. Note slight muscular atrophy of the hands. C. Boy, aged 27. Note: Hearing aid.|left Alpha-mannosidosis is a lifelong multi-systemic progressive disease, with neuromuscular and skeletal deterioration over decades. The timing of the appearance of symptoms correlates with the severity of the disease. The onset of the most severe form of the disease occurs within the first months of life and involves skeletal abnormalities and intellectual disability, with rapid progression leading to death from primary central nervous system involvement or myopathy. However, most neonates with lysosomal storage disorders are asymptomatic and only rarely severely affected. This delays diagnosis, particularly as milder forms of the disease involve only mild to moderate intellectual disability, which progresses gradually during childhood or adolescence.