The Harvard Medical School Genetics Training Program is accredited by the American Board of Medical Genetics to provide training in Clinical Biochemical Genetics. Participating laboratories are at Children's Hospital, Massachusetts General Hospital, and the University of Massachusetts New England Regional Newborn Screening Program.

The overall goals of the biochemical genetics program are:

• become familiar with the diagnosis, management and natural history of major inborn errors of metabolism
• learn how to perform and interpret laboratory tests used in the diagnosis of metabolic disorders
• understand the principles and practice of newborn screening
• appreciate the issues in quality assurance necessary to management of a diagnostic laboratory
• become sensitive to ethical issues in genetics
• participate in an ongoing research activity in biochemical genetics

The following is a sample schedule of the biochemical genetics program. Click on the laboratories to view a description.

Description of Training Sites

Children's Hospital, Boston

Biochemical genetics at Children's Hospital consists of an active inpatient consultation service and two weekly outpatient clinics. The busy service provides an opportunity for assessing children with a wide variety of metabolic disorders, including defects of amino acid and organic acid metabolism, disorders of carbohydrate metabolism, fatty acid oxidation defects, lysosomal storage diseases, inborn errors of peroxisomal metabolism, and defects in mitochondrial energy metabolism.

The inpatient service manages patients with identified inborn errors (usually in metabolic crisis), and consults on children with suspected metabolic disease on the general medical wards and in the neonatal and pediatric intensive care units at Children’s Hospital, and the high risk perinatal intensive care units at neighboring Beth Israel-Deaconess Medical Center and Brigham and Women's Hospital. In addition, patients with documented or suspected inborn errors may be admitted to the clinical research center for specialized evaluation under individual research protocols.

The outpatient service sees over 900 patient visits per year in two outpatient clinics per week. About 45% of clinic visits involve patients with metabolic disorders which are known to be associated with episodes of acute clinical decompensation. Patients with PKU and other disorders without life-threatening complications comprise another 40% of visits. The clinic also sees most of the newborns identified by the New England Regional Screening Program as having an inborn error of metabolism.

Additional Rotations

MD trainees spend 6 weeks on call for inpatient consults. Ph.D. trainees fulfill this requirement in an observational capacity. Trainees also attend the Lipid Clinic under the direction of Ellis Neufeld, MD, Ph.D.

Massachusetts General Hospital

This laboratory and its clinical component provide diagnosis, follow-up, and treatment for disorders of amino acid and organic acid metabolism.

The laboratory occupies approximately 1500 square feet of space within the Neuroscience Center research complex of the MGH. Laboratory equipment includes an amino acid analyzer, HPLC system, fraction collector, gas chromatograph/mass spectrometer, gel electrophoresis apparatus, thermocycler, UV transilluminator and photography system, liquid scintillation counter, UV/VIS recording spectrophotometer, ultracentrifuge, and other small equipment. The laboratory performs metabolic screening including quantitative amino acid analyses and related metabolite testing, organic acid analyses and carnitine determination. Radioisotopic and spectrophotometric assays are performed for a number of enzymes involved in intermediary metabolism including biotinidase, the urea cycle enzymes, ornithine aminotransferase, and fumarase. DNA diagnosis of medium chain acyl CoA dehydrogenase deficiency and methylene tetrahydrofolate reductase thermolabile polymorphism is offered, as is prenatal testing for selected metabolic disorders. A total of approximately 2,500 tests are performed each year at this laboratory.

The clinical component of the laboratory also serves as a referral center for the diagnosis and treatment of patients with amino acid or organic acid disorders. Patient visits are at the weekly Metabolic Disorders Unit. Patients needing hospitalization are admitted to the Pediatric or Neurology Services of the MGH under the care of Dr. Shih. Metabolic consultations are also covered.

This unit is actively engaged in research. Current areas of interest include the molecular characterizations of homocystinuria due to cystathionine b-synthase deficiency and fumarase deficiency and a search for the enzyme defect in D-2-hydroxyglutaric aciduria. Other ongoing studies are the evaluation of long-term outcome in both treated and untreated amino acid disorders, the delineation of defects in newly discovered disorders, and the effects of maternal inborn errors on the mother and offspring.

Additional Rotations

Fellows attend four sessions of the Hypoglycemic Clinic in the Lipid Metabolism Unit, directed by Mason Freeman, MD, during their MGH rotation.

Massachusetts State Laboratory
New England Regional Newborn Screening Program

This program performs screening tests for inborn errors of metabolism on over 80,000 newborns per year from Massachusetts. Samples are also collected from newborns in all of the other New England states except Connecticut. The inborn errors screened include PKU, galactosemia, maple syrup urine disease, homocystinuria, and biotinidase deficiency. Specimens are also screened for congenital hypothyroidism and congenital adrenal hyperplasia.

The program occupies over 4,000 square feet of space in the State Laboratory Institute of the Massachusetts Department of Public Health and consists of laboratories, offices, and conference rooms. The laboratories are equipped for a full complement of enzyme assays, radioimmunoassays, enzyme immunoassays, tandem mass spectrometry, and molecular genetics analysis. The molecular studies are for cystic fibrosis and galactosemia. Also included in the Newborn Screening Program are laboratories for screening congenital toxoplasmosis.

The program serves not only for newborn screening in New England, but is also a referral center for biochemical genetics throughout New England and other parts of the United States and abroad. In addition, the program conducts research in the techniques and results of newborn screening.