Gerard Berry, PhD
|Hospital Title||Director, Metabolism Program|
|Academic Title||Professor of Pediatrics|
300 Longwood Avenue
Boston, MA 02115
Our lab is developing state-of-the-art diagnostic tests and more effective therapies for patients with galactosemia, a genetic disease that is caused by the lack of an enzyme required to convert galactose into glucose, the primary energy source of our cells. The major source of galactose is the disaccharide lactose, found in milk and dairy products.
Galactosemia usually causes no symptoms at birth, but jaundice, vomiting and cataracts develop with progressive exposure to lactose, and affected babies fail to gain weight. If undetected, classic galactosemia results in liver disease, hemorrhage, brain swelling and usually death in the first few weeks of life. Even with dietary lactose restriction, patients with the most severe and most common form of the disease still manifest cognitive deficits, speech deficits, reduced bone mineral density and, in females, primary ovarian insufficiency.
More sensitive tests
Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we are creating new tests to more accurately determine the levels of activity of the enzymes deficient in the three types of galactosemia. To date, we have developed tests to measure GALK and GALT, the enzyme deficient in the most common form of galactosemia. We are now using these tests in a national observational study of patients with galactosemia to establish genotype-phenotype correlations, to better diagnose the milder variant forms and to predict outcomes of patients suffering all forms of the disease. In the future, we plan to use the GALT enzyme assay to monitor the effectiveness of a novel gene therapy-based treatment strategy, in collaboration with George Daley, MD, PhD.
An improved animal model
Several studies have shown that during the newborn period, galactosemic infants may also have reduced brain levels of myo-inositol, a critical signaling component. To determine whether the lack of myo-inositol underlies the cognitive deficits that develop in galactosemia, we generated SMIT1 knockout mice, which exhibit a marked (92 to 96 percent) reduction in myo-inositol in the brain. We are now studying these mice to investigate how a myo-inositol deficiency in the fetal brain leads to faulty neuronal circuitry and, potentially, to intellectual disability.
About Gerard Berry, MD
Gerard Berry, MD, is one of the nation's leading specialists in the study and treatment of galactosemia. He is director of the Metabolism Program at Boston Children's Hospital and a Professor of Pediatrics at Harvard Medical School.
He received his MD from Jefferson Medical College in Philadelphia. He then completed his residency in pediatrics at Thomas Jefferson University and a fellowship in biochemical genetics and pediatric endocrinology at the Children's Hospital of Philadelphia. He is board certified in biochemical genetics, pediatrics and pediatric endocrinology.
Li Y et al. Quantification of galactose-1-phosphate uridyltransferase enzyme activity by liquid chromatography-tandem mass spectrometry. Clin Chem 2010 May; 56(5):772-80.
Buccafusca R et al. Characterization of the null murine sodium/myo-inositol cotransporter 1 (Smit1 or Slc5a3) phenotype: myo-inositol rescue is independent of expression of its cognate mitochondrial ribosomal protein subunit 6 (Mrps6) gene and of phosphatidylinositol levels in neonatal brain. Mol Genet Metab 2008 Sep-Oct; 95(1-2):81-95.
Berry GT et al. The rate of de novo galactose synthesis in patients with galactose -1-phosphate uridyltransferase (GALT) deficiency. Mol Genet Metab 2004 Jan; 81(1):22-30.
Berry GT et al. Loss of murine Na+/myo-inositol cotransporter leads to brain myo-inositol depletion and central apnea. J Biol Chem 2003 May 16; 278(20):18297-302.
- Berry GT et al. Galactose breath testing distinguishes variant and severe galactose-1-phosphate uridyltransferase genotypes. Pediatr Res 2000 Sep; 48(3):323-8.