Response to ACMG Practice Guidelines and ACMG Standards and Guidelines, Genetics in Medicine, July 2010, volume 12, number 7, pages 446–463 and 464–470

To the Editor:

I enjoyed reading the two documents by the standards committee in collaboration with Dr. Kishnani and her associates.¹ This is a well laid out document and provides excellent guidelines for the management of children with type III glycogen storage disorder (GSD III).

One item worth commenting on is the mention of cardiomyopathy that occurs in some patients with GSD III. As mentioned by the authors, this is a complication that may occur over time despite recommended therapy with good compliance.

I would like to relay my experience with a patient who highlights this particular phenomenon. The clinical events with this patient potentially provide some insight into this problem. This patient is a white male with GSD III who was managed from 11 months of age with a high-protein/low-carbohydrate diet through frequent feeds during the day and a continuous nocturnal drip with high-protein liquid formulas. (Although current standards involve the use of cornstarch and high-protein supplementation—not necessarily by continuous infusion—this has not always been the case. Single-mode therapy was prescribed for this patient in the 1980s). As he was followed up, frequent assessments of liver function consistently showed mildly elevated levels of these parameters. At approximately 10 years of age, the patient requested a switch to cornstarch to avoid the inconvenience of the nighttime drip. This change was made at his/his family's request. Notably, a dramatic rise in CK levels with no change in liver function studies were noted after this change, with a rise in the MB fraction. After just a couple months of cornstarch treatment, his therapy was returned to high-protein feeds with the discontinuation of the cornstarch. Commensurably, his CK levels returned to baseline. Also, the MB fraction returned to a nonalarming state. Cardiac imaging studies were not performed before or after this occurrence (Table 1).

Table 1 Enzyme levels with changes in therapy

I send this letter to share this experience with others who care for these patients. The changes that were observed were dramatic. For this patient, it seems that some difference in the cornstarch regimen, when compared with the high-protein therapy was responsible for accentuating a cardiomyopathy. I recognize that from the perspective of a single case report, no firm conclusions can be drawn nor can any specific recommendations be made. More cases and systematic study would be needed to determine whether this is phenomenon, which might be seen in additional patients.