Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Alpha-Mannosidosis

What is Alpha-Mannosidosis?

• Alpha-mannosidosis is a form of lysosomal storage disorder which results in a deficiency of the enzyme alpha-D-mannosidase
• This is a lifelong illness that impacts multiple body systems
• Symptoms of the disease progressively worsen over time
• There are three proposed subtypes of alpha-mannosidosis:
  • Type 1: This is the mildest form with the slowest progression, which is typically diagnosed after age ten
  • Type 2: The moderate form and most common form, with symptoms onset before age ten
  • Type 3: The most severe form, which usually results in an early death
• Alpha-mannosidosis was first described in 1967

How Do You Get It?

• Alpha-mannosidosis is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene in order to pass along the disorder
  • If both parents are carriers, the chance of passing along two copies and causing the disease is 25 percent
  • There is also a two in three chance that unaffected siblings will be carriers.
• A variety of mutations have been documented in alpha-mannosidosis
  • As a result, the three types of the disease are still considered speculative; the range of severity follows a spectrum.

What Are the Symptoms?

• Symptoms of alpha-mannosidosis can range greatly in severity but may include:
  • Distinct facial features (Flattened nasal bridge, prominent forehead, round eyebrows)
  • Intellectual disability
  • Skeletal abnormalities
  • Myopathy
  • Recurrent infections
  • Psychomotor delays
  • Hearing impairments

How Is It Treated?

• There is no cure for alpha-mannosidosis
• Treatment is often proactive in nature and attempts to mitigate the effects of emerging complications
  • These approaches are aimed to address the impacts of symptoms and do not impact disease progression
• Stem cell transplantation can be useful for some patients and is more useful in young patients
• An enzyme replacement therapy is approved for use in the EU

Where Can I Learn More???

• Learn more about this disease from the MPS Society.
• Check out our cornerstone on this disease here.