Clinical Trials

Acetazolamide Efficacy in Ataxia in PMM2-CDG – Eva Morava-Kozicz, Mayo Clinic

Objective 1 (Primary): To determine the efficacy of acetazolamide in improving ataxia in patients with PMM2-CDG.

Objective 2 (Secondary): To evaluate for any adverse events related to longer term acetazolamide administration.

Objective 3 (Secondary): To examine the effect of acetazolamide on PMM2 biomarkers including carbohydrate deficient transferrin results, electrolytes (Na, K, Cl, CO2), VBG (pH, pCO2, PO2, CO2, Base excess), liver function tests (AST, ALT, GGT, indirect and direct bilirubin, total protein, albumin, alkaline phosphatase), kidney function tests (BUN, Creatinine, Urinalysis, urine calcium/creatinine ratio, urine protein/creatinine ratio), growth (height, weight, head circumference), vital signs (blood pressure, respiratory rate, heart rate), PROMIS scores, dysarthria using the PATA score, and NPCRS score.

Objective 4 (Secondary): To explore characteristics of individuals with PMM2-CDG who do not respond to acetazolamide.

Natural History Study Protocol in PMM2-CDG (CDG-Ia) – Glycomine, Inc.

Subjects enrolled in this natural history study will be thoroughly examined for signs and symptoms of PMM2-CDG. Medical history, physical examination, laboratory testing and imaging studies will be performed during a single consultation. Follow-up will occur every 6 months at a minimum, depending on the standard of care at the investigator’s institution as well as the clinical status of the individual patient. All medical procedures are routine. No new therapy is offered as part of this study, and no change in the patients’ routine therapy is dictated by this protocol. No randomization will be performed.

All serious and non-serious adverse events will be recorded in the study CRF database.

Clinical and Basic Investigations Into Congenital Disorders of Glycosylation – Eva Morava-Kozicz, Mayo Clinic

The investigators are conducting a natural history study of patients with congenital disorders of glycosylation (CDG). The study will look into the progression of the disease amongst the participants and also look at the clinical symptoms and how they vary amongst different diseased population groups. The participants will be asked to fill out questionnaires either on their own or with a provider that will grade the severity of disease and document symptoms and diet. Participants will have an opportunity to submit blood, urine, and stool samples that will be tested for biomarkers for CDG.

Participants will also complete dietary food records, physical exams, CDG scores, and the PROMIS questionnaires to assess disease progression and severity.

Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation – Eva Morava-Kozicz, Mayo Clinic

Researchers are trying to assess whether the use of simple sugars given as a daily dietary supplement can improve the health of children with congenital disorders of glycosylation (CDG).

The goal of this study is to collect data from patients diagnosed with congenital disorders of glycosylation and taking a simple sugar supplement. The study team wants to expand the evidence on the beneficial effects of this treatment in clinical practice.

Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation – National Institutes of Health (NIH)

Congenital disorders of glycosylation (CDGs) are a group of diseases characterized by an abnormal glycosylation of proteins, but that can also result from an abnormal synthesis of glycosaminoglycans, glycophospholipids or glycosylphosphatidylinositol or the abnormal synthesis or utilization of dolichols. CDGs were first described in 1980, but the initial description of mutations in a gene underlying CDGs did not occur until 1997. Since then, there has been a rapid discovery phase of new CDGs, with more than 80 different types, reflecting defined mutations in 80 different genes in glycobiologic pathways affecting about 1000 patients worldwide. The clinical manifestations of CDGs are quite variable both within and among different types, and physicians from every specialty will likely encounter patients affected by glycosylation defects. The diagnosis of CDGs should be suspected in cases with neurological signs and symptoms of unknown etiology, or in any patient with multisystemic disease even in the absence of neurological features. Other potential clinical presentations include tissuespecific disorders such as anemia or ichthyosis, when common disorders have been ruled out. Diagnostic screening for many of the disorders is performed by analyzing the glycosylation on serum transferrin, initially by isoelectric focusing, now by mass spectrometry, in specialized clinical diagnostic laboratories both in the United States and abroad. The pattern of transferring glycoforms allows the differentiation between defects of Nglycosylation assembly in the ER (type I) and defects of Nglycan trimming and elongation, occurring mainly in the Golgi apparatus (type II). Most recently, wholeexome sequencing has led to the elucidation of the underlying mutation in patients with unknown CDGs. Treatment is available for only three CDG subtypes. In this protocol, we propose to clinically evaluate up to 100 patients of all ethnicities with known or suspected CDGs, obtain cells, plasma, and urine for future studies, perform mutation analysis for known CDGcausing genes, and search for other genes responsible for CDGs. Routine admissions of 3-5 days will occur annually or as required by changes in clinical symptomatology.

Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism – Eva Morava-Kozicz, Mayo Clinic

Researchers are trying to determine the efficacy of a global metabolomic approach in testing for and diagnosing inborn errors of metabolism as opposed to traditional testing methods.

Residual samples will be tested for a variety of biomarkers that may lead to better understanding of these disorders and help develop treatment options.

Galactose Supplementation for the Treatment of MOGHE (GATE) – Angel Aledo-Serrano, Hospital Ruber Internacional

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new entity frequently associated with refractory epilepsy and neurodevelopmental disorders. Recently, it has been associated to SLC35A2 (Solute Carrier Family 35 Member A2) brain mosaic pathogenic variants. In addition, patients with germline SLC35A2 pathogenic variants improve with galactose supplementation. Therefore, the investigators aim to elucidate whether d-galactose as an add-on treatment might improve epilepsy and developmental outcomes in patients with MOGHE.

SARS-COV2 Pandemic Serosurvey in a Rare Disease Population – National Institutes of Health (NIH)

The SARS-COV2 (COVID-19) outbreak has had a major impact on the economy and society. Researchers want to learn how widespread the infection is in the rare disease community. To do this, they will get blood samples from people with rare diseases. They will use at-home sampling. This will allow them to get samples from people across a wide area. To estimate the proportion of people with rare diseases who have SARS-COV2 antibodies in the National Center for the Advancement of Translational Sciences Rare Disease Clinical Research Network (RDCRN) Rare Diseases Survey over time. Participants will be sent a home kit to collect a blood sample.