Clinical Trial: Unrelated Donor BMT for Treatment of Patients With PGK Deficiency

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Unrelated Donor Bone Marrow Transplantation for Definitive Treatment of Patients With Phosphoglycerate Kinase (PGK) Deficiency

Brief Summary:

Phosphoglycerate kinase (PGK) deficiency is a rare x-linked disorder characterized by hemolytic anemia, seizures, muscle fatigue, and progressive neurological dysfunction. The disease is caused by the deficiency of PGK, an enzyme required for ATP formation through the glycolytic pathway. PGK is an enzyme that is ubiquitous to all cells of the human body, but red blood cells, muscles, and nerve cells are most severely affected by the absence of PGK due to their reliance upon the glycolytic pathway. Mutations of the PGK gene are highly variable and result in diverse phenotypes, ranging from mild hemolytic anemia only to severe mental retardation and early death in childhood. The more severe phenotypes show progressive neurologic deterioration between infancy and adolescence.

This is a 2 patient study aimed at studying the role of stem cell transplant in PGK deficiency. Because the disease is so rare, the study will be limited to the 2 sibling patients followed by our group, though it would be open to other participants who would meet inclusion/exclusion criteria if such presented to us. The objective of this study is to evaluate the feasibility and efficacy of stem cell transplants to treat patients with PGK deficiency, Amiens subtype.

Detailed Summary:

Phosphoglycerate kinase (PGK) deficiency is a rare x-linked disorder characterized by hemolytic anemia, seizures, muscle fatigue, and progressive neurological dysfunction. The disease is caused by the deficiency of PGK, an enzyme required for ATP formation through the glycolytic pathway. PGK is an enzyme that is ubiquitous to all cells of the human body, but red blood cells, muscles, and nerve cells are most severely affected by the absence of PGK due to their reliance upon the glycolytic pathway. Mutations of the PGK gene are highly variable and result in diverse phenotypes, ranging from mild hemolytic anemia only1 to severe mental retardation and early death in childhood.2-5 The more severe phenotypes show progressive neurologic deterioration between infancy and adolescence.2,3,5 PGK-Amiens refers to a particular mutation that is an A to T transversion, which predicts an amino acid change of aspartate (Asp: GAT) to valine (Val: GTT) at the 164th position from the NH2-terminal methionine residue. This D164V mutation has been identified previously as PGK-Amiens or PGK-New York in a French and in a Chinese family respectively.3,6 This particular mutation results in the most severe phenotype. All 6 of the boys described in the literature with this mutation have had progressive neurologic decline, seizures, episodes of hemiplegia, aphasia, emotional lability, and severe hemolytic crises. Two of the boys died in childhood, 2 are institutionalized with no ability to communicate or provide self-care, and 2 are moderately mentally retarded with seizures and hemolytic anemia. The two brothers cared for at this institution have the Amiens variant of PGK deficiency.

Allogeneic bone marrow transplantation (BMT) became feasible in the 1960s after elucidation of the Human Leukocyte Antigen (HLA) complex. Since then, the therapy has evolved into an effective therapy for many hematologi
Sponsor: Vanderbilt University

Current Primary Outcome: To evaluate the feasibility and efficacy of stem cell transplants to treat two patients with PGK deficiency, Amiens subtype. [ Time Frame: 5+ years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Vanderbilt University

Dates:
Date Received: December 26, 2007
Date Started: June 2006
Date Completion:
Last Updated: November 22, 2016
Last Verified: November 2016