MDC1A: small changes with a huge impact

The muscle disease Merosin-Deficient Congenital Dystrophy type 1A, MDC1A for short, belongs to the so called congenital neuromuscular diseases. These are diseases that affect the muscles and their direct nervous system control. MDC1A affects 1 to 4 people in every 100.000, making it a rarely occurring disease which limits the support for research and experience of physicians with patients.

 

Low muscle tone and muscle weakness

MDC1A is a hereditary muscle disorder often noticed at birth or within the first few months of life. MDC1A is sometimes referred to as LAMA2-related muscular dystrophy. In MDC1A, mutations in the LAMA2 gene cause the abnormal production of the protein Laminin 𝛼2. This protein fulfills important functions within the muscle. It particularly maintains structural interaction between the muscle cells and the surrounding tissue, essentially holding the muscle in place. When the protein’s function is impaired, it causes patients to suffer from low muscle tone and muscle weakness at birth. Furthermore, some children develop feeding and breathing problems, as well as a delay in motor skill development.

Milestones

Babies with MDC1A often appear floppy and may not move as much as other babies. Children with MDC1A reach motor milestones later than other children and only a very small proportion of children with MDC1A are able to walk independently. Muscle weakness does not tend to rapidly progress and motor function remains relatively stable throughout childhood. When children reach puberty however, and grow taller and heavier, children might experience additional difficulties. Children may develop, or be born with, contractures.

A very common problem in children with MDC1A is weakness of the respiratory muscles, which results in frequent chest infections and poor breathing at night. Respiratory issues usually stabilize or improve in the first few years. In adolescence however, respiratory function may begin to decline. Most children with MDC1A also develop a curvature of the spine (scoliosis). Another frequent problem is feeding difficulties and the accompanied weight loss. In the worst cases patients die in childhood.

Current treatment

A cure is not yet available and the current treatment only alleviates the symptoms. Physiotherapy can help prevent the ‘contractures’, children may develop or are borne with, and a programme of exercises should be worked out with a physiotherapist very soon after diagnosis, but surgery is often eventually required to release contractures. It is important to monitor respiratory function during the night and children may need to use a ventilator at night with a special facial or nasal mask. For some patients this is insufficient and a tracheostomy is needed. Respiratory issues usually stabilise or improve in the first few years, but, in adolescence however, respiratory function may begin to decline requiring more ventilator support. It is important to make sure that children with MDC1A are well nourished. Often the swallowing muscles are weak and feeding supplements are needed.

New forms of treatment

Because there is no cure yet, researchers are currently looking into new forms of treatment. One idea is to withdraw stem cells from patients themselves, exchange the mutated gene with a healthy version and re-inject the cells into the patients. The altered cells will generate new, healthy muscle, counteracting the muscle weakness for an extended period of time. Another approach may be to target the affected cells directly by using a virus. This virus shuts down the production of defective proteins and activates a replacement protein, which takes over the role of Laminin 𝛼2. Drug treatments that buffer the muscle loss caused by genetic mutations are also an option that is currently being explored and could be combined with other therapies. While these options are promising, more research and communication between experts is needed to improve their efficacy and implement them into the standard treatment plan for MDC1A.

 

 

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