MAT Deficiency: Wider effects of a rare disease

A case of a rare childhood disease reveals a new mutation as underlying cause and  identifies unknown manifestations of the disease on the skin and hair.

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Researchers at KAIMRC have established a link between a rare childhood disease and a newly identified gene mutation, as well as previously unknown complications.  

“This is the latest of more than 50 novel genes associated with diseases that we have discovered in the last few years,” says Majid Alfadhel, explaining how the research fits into a long history of achievement in the field of genetic disease.

This latest work focused on a single specific case of a 40-month (3-year) old patient suffering from methyl adenosyltransferase I/III deficiency (MAT deficiency). This metabolic disease occurs in children whose genome has a mutation in the gene for the methyladenosyltransferase enzyme. The resulting deficiency in the enzyme leads to an accumulation of the amino acid methionine in blood. Methionine is required to make many of the body’s normal proteins, but too much can be harmful. Most cases of MAT deficiency nevertheless lead to minimal symptoms, like a distinct breath odour, but some severe cases are associated with neurological problems like impaired movement and intellectual disabilities. 

One of the most significant results of the KAIMRC research is to identify symptoms beyond the disease’s effects on the central nervous system.  

“Our patient had an unexplained zinc and iron deficiency, in addition to mild speech delay,” says Alfadhel. These problems were accompanied by skin lesions, hair whitening and hair loss. 

The scientists identified the genetic cause of the 40-month old male’s MAT-deficiency as a previously unidentified mutation in the gene for the MAT enzyme. This adds to the range of mutations that can cause the disease. 

“As we conducted our research we were surprised by the lack of knowledge about this rare disease,” says Alfadhel. One major recommendation emerging from the investigation is that patients diagnosed with MAT-deficiency should be further screened in search of the less well-known consequences of the condition, beyond its effects on the central nervous system. 

In an effort to clarify what is known about these wider symptoms, the researchers reviewed previous reports of the consequences of the disease. They found that the reporting of symptoms other than effects on the central nervous system was “sporadic”. 

“Investigating effects of the disease beyond the central nervous system might lead to a better understanding of the disease and the function of the MAT enzyme,” says Alfadhel. 

With the KAIMRC team having looked at just one case, they emphasize that a much wider survey of cases from around the world would now be justified to yield deeper insights. 

References

  1.  Nashabat, M., Al-Khenaizan, S. & Alfadhel, M. Methionine adenosyltransferase I/III deficiency: beyond the central nervous system manifestations. Therapeutics and Clinical Risk Management 14, 225 – 229 (2018) | article

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