Congenital disorders of glycosylation (CDG) are a large group of rare, inherited disorders that affect a complex process in the body called glycosylation. Most children who are diagnosed with CDG have neurological issues and symptoms, developmental problems, growth delays, and problems with organs not working like they should. PMM2-congenital disorder of glycosylation (PMM2-CDG) is the most common type of CDG.
Here, we speak to two parents of children diagnosed with PMM2-CDG—Heather Franklin (mother of Michaela, age 13, and Nathaniel, age 11) and Bobbie List (mother of Danielle “Dee,” age 21)—about their journey as caregivers and advocates for children with a rare disease.
When and how were your children diagnosed?
Franklin: Michaela began showing signs of delay from birth, including trouble with breast feeding, strabismus, and developmental delays—she could not hold her head up straight without wobbling until about 14 months. At 6 months she was referred to a geneticist, neurologist, and ophthalmologist, as well as early childhood intervention, magnetic resonance imaging, and physical therapy. We struggled with testing for the next two years.
After a muscle biopsy and nerve conduction study, we were referred to a neuromuscular specialist, Dr. Castro, at Dallas Children’s. Shortly after, we received the official diagnosis. In this time, Nathaniel had been born and was also showing similar delays. After Michaela’s test came back positive, they tested Nathaniel as well. At the time of diagnosis, Michaela was about 2.5 years old and Nathaniel was about 7 months old.
List: Dee was diagnosed when she was 11 months old. She was born four weeks early at 4 lbs. and 10 oz. She struggled with gastrointestinal issues and had low muscle tone. She began missing developmental milestones and was admitted into the hospital with failure to thrive at 6 months old. We were referred to a geneticist and neurologist. The geneticist in Cleveland ran a blood test and confirmed CDG. A follow up skin biopsy confirmed the PMM2 enzyme deficiency. A later MRI further confirmed cerebellar hypoplasia.
What has been your experience as a family member of a person living with a rare disease?
Franklin: Our experiences have been wide. At first diagnosis, we struggled with reality, going through the stages of grief. My husband and I traveled this path at different rates and our marriage relationship had to try and keep up. For me, this process lasted a couple of years. I remember at one point being extremely bitter and resentful towards other young families who “had perfect children.” At this point in our lives, all of our friends were also raising young families, and my biggest struggle was maintaining my composure when others would brag about their children’s progress—“Billy climbed the monkey bars and did a flip today”… while my children were struggling to eat solid foods and had endless hours of therapy and doctors’ appointments.
Eventually, the resentment and bitterness passed, and I began to focus more on just trying to do my best for my family and enjoy the hidden blessings God has rained down upon us in this situation. Our life today still consists of many hours of therapies and doctors’ appointments each month—as well as moments of grief when we hit a setback or reality tries to slap at us again. It is a lonely life, with little time and energy for adult friendships and relationships. However, our marriage is strong, and our family loves each other fiercely. We live each day at the pace of the children, focusing on the positive moments as much as possible, and enjoying the life we have been given.
List: We were fortunate that we were able to start early intervention services when Dee was 7 months old. By getting her diagnosis early, we were able to coordinate appointments with specialists from hematology, orthopedics, cardiology, neurology, endocrinology, and gastroenterology to begin establishing a care plan. We believe the coordinated specialists and access to early interventional services such as speech, physical therapy, and occupational therapy enabled Dee to achieve the milestones that she has to date.
Our geneticist told us to allow Dee to be her own guide—allow her to show us what she would be capable of instead of us telling her what she wouldn’t be able to do. Dee is fully vocal, attended high school and post-secondary school, and plays adaptive baseball, swimming, and bowling. She is also a cheerleader.
How did you get involved in research?
Franklin: We met Dr. Morava at the CDG conference in California in 2020 and were officially enrolled in the natural history study a couple of months later. This progressed to more therapy studies over the next couple of years at Children’s Hospital Colorado.
List: We attended the CDG Conference in 2020 and met Dr. Edmondson from Children’s Hospital of Philadelphia. We live outside of Pittsburgh, and he agreed to take on Dee’s care coordination. Through Dr. Edmondson, we were introduced to the natural history study, as well as the acetazolamide trial.
In May 2021, Dee started the acetazolamide blind trial and began taking the actual medication in November 2021. Unfortunately, Dee began to experience side effects that were proving more disruptive when compared to the incremental improvements we had seen while on the medication. Our family decided to stop the acetazolamide in January/February.
How has research made an impact in your lives?
Franklin: Being a part of the acetazolomide study has given my son many benefits. His speech is much better, as well as digestion, memory, and fine motor skills. As far as the natural history study, we as a family have not seen many benefits, just tests. However, we are grateful to be closer to other families we have come to know in the CDG community. We know that by having our children as part of the natural history study for CDG, we are helping further the research in knowing more about this complicated group of disorders. We are also extremely grateful for the medical professionals that are focused on CDG and can help us navigate this path with our children.
List: Although the acetazolamide was not a success for Dee, we know that other families have seen improvements. We attended our first conference when Dee was 4 years old. At that time, the focus was still on physician awareness of clinical signs, identification of CDG types, and early diagnosis so that therapies could be started to help manage symptoms. In the last two years, we have now heard of three to five clinical trials to treat the root cause for the disease rather than just symptom management.
The CDG community is a wonderful resource to share information, console each other in difficult times, and celebrate the small victories. The value of being able to provide hope for new families receiving a CDG diagnosis cannot be measured! As Dee gets older, we have also been relying on those families who have paved the way before us. Now that Dee is “stable,” we find ourselves looking for help on things like living with CDG into adulthood—health issues to be most worried about, living and working as independently as possible, trusts and executorships, and sibling genetic testing. As research helps us learn about CDG (and rare diseases in general), we hope that information will be translatable from birth through adulthood.
The Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) is part of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). FCDGC is funded under grant number U54NS115198 as a collaboration between NCATS, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the Office of Dietary Supplements (ODS).