Science Saturday: Physicians have new guidelines for managing rare genetic, metabolic disorders

Science Saturday: Physicians have new guidelines for managing rare genetic, metabolic disorders

By
Susan Murphy

February 6, 2021

Physicians now have a blueprint for diagnosing and managing two specific rare inherited metabolic diseases within a group of nearly 150 congenital disorders of glycosylation. These diseases can cause serious and sometimes fatal malfunctions of several organs at or before birth, as well as chronic debilitating symptoms in adults.

The consensus guidelines were published in the Journal of Inherited Metabolic Disease by a team of international experts with the Frontiers in Congenital Disorders of Glycosylation Consortium. This consortium is led by Eva Morava-Kozicz, M.D., Ph.D., a physician scientist in Mayo Clinic's Department of Clinical Genomics.

Dr. Morava-Kozicz conducts translational research in congenital disorders of glycosylation and mitochondrial disorders, and is developing dietary therapies in genetic disorders.

"We aim to continue establishing more guidelines for the diagnosis and treatment of different metabolic disorders types," says Dr. Morava-Kozicz. "Our goal is to expand the available knowledge for anyone who meets our patients and unify optimal care."

Congenital disorders of glycosylation is an umbrella term for a rapidly expanding group of rare genetic, metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins. They typically present as multisystemic disorders with a broad clinical spectrum, including, but not limited to, developmental delay, an abnormally low level of muscle tone, abnormal brain development, heart and liver manifestations, and hemorrhaging or clotting disorders.

"Neurological abnormalities are frequently present," explains Dr. Morava-Kozicz. "There is considerable variation in the severity of this group of diseases ranging from a nonprogressive, chronic presentation in adults to severe multiorgan dysfunctions causing infantile death."

The new published guidelines focus on two specific treatable congenital disorders of glycosylation:

Mannose phosphate isomerase (MPI-CDG)
This disorder is a rare subtype of congenital disorders caused by pathogenic variants in the mannose phosphate isomerase gene.

Phosphoglucomutase 1 (GM1-CDG)
This disorder affects glycogen metabolism, glycolysis and protein glycosylation.

Guidelines suggest both disorders can be effectively treated and improve many patients' symptoms.

To create the guidelines, the consortium assembled congenital disorders of glycosylation experts around the world. Physicians, scientists and researchers conducted full literature reviews of all case reports published on the two congenital disorders of glycosylation. The resulting guidelines are based on the best available evidence-based data and expert opinions.

"Knowledge share is essential in rare disorders," says Dr. Morava-Kozicz. "Within a year, we enrolled more than 70 patients to the study to learn more about this rare disease group and empower patients by metabolic and genetic education. This was only possible with the continuous support of the patient association CDG Care."

The Frontiers in Congenital Disorders of Glycosylation Consortium is part of the Rare Diseases Clinical Research Network, which is funded by the National Institutes of Health and led by the National Center for Advancing Translational Sciences through its Office of Rare Diseases Research. The Frontiers in Congenital Disorders of Glycosylation Consortium is funded under grant U54NS115198 as a collaboration between National Center for Advancing Translational Sciences, the National Institute of Neurological Disorders and Stroke, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Office of Dietary Supplements.