Clinical Biochemical Genetics

The Clinical Biochemical Genetics Training Program at Harvard Medical School began in 1982.  At that time, it included the following: The Clinical Metabolic Program at Children's Hospital Boston; the Metabolic Laboratory and Clinic at the Massachusetts General Hospital; and the New England Newborn Screening Program at the State Laboratory Institute of the Massachusetts Department of Public Health. In 1986 it was incorporated into the HMS Training Program in Medical Genetics and continues in that capacity.  In the beginning the emphasis was on training physicians to become specialists in biochemical genetics but when it was incorporated into the HMS Medical Genetics Training Program, the goal was expanded to include providing medical geneticists with competence in clinical biochemical genetics.  The Program was recently further expanded to provide specific biochemical genetic training to non-physicians who wish to meet the requirements for the Clinical Biochemical Genetics section of the ABMG.

The training objectives include: (1) acquiring knowledge of the clinical, biochemical and molecular features of biochemical genetic disorders; (2) becoming familiar with the treatments specific for the biochemical genetic disorders; (3) becoming familiar with laboratory analysis such as those for amino acids, organic acids, and acylcarnitines; (4) learning the biochemical features that determine the diagnosis in specific biochemical genetic disorders; (5) becoming familiar with newborn screening methodologies for metabolic disorders; (6) learning the newborn screening analyte abnormalities that are associated with the biochemical genetic disorders; (7) developing familiarity with and becoming sensitive to the ethical issues of newborn screening; (8) becoming skillful in communicating biochemical genetic findings to referring physicians; (9) participating in research activities in biochemical genetics; and (10) non-physician fellows develop expertise in the technical aspects of analyses for a diagnostic biochemical genetics laboratory, including test development, quality control and quality assurance, as well as supervisory roles.

There are three Clinical Biochemical Genetics laboratories associated with the program. The Children's Hospital Metabolic Laboratory, the Amino Acid Lab at Massachusetts General Hospital and the New England Newborn Screening Program.

Fellows spend two days per week in whichever lab they are rotating through, participating in analyses and weekly lab meetings. Each fellow is required to rotate through both the Children's Hospital Metabolic Lab and the MGH Neurochemistry and Amino Acid Laboratory. There is an option to do a rotation at the New England Newborn Screening Program to participate in the usual screening procedures. Each fellow is responsible for developing a new clinical test, with all of the appropriate validation procedures.

At Children's Hospital the fellows learn the principles of sample preparation and analysis for amino acids in blood, urine and CSF by the automated HPLC-based amino acid analyzer. They observe the extraction and analysis methodology for urine organic acid and acylglycine analysis by gas chromatography/mass spectrometry and analyte identification by searching and matching to known sample characteristics in available libraries. They also observe and become familiar with tandem mass spectrometry analysis of plasma acylcarnitines. They meet twice weekly with Dr. Marsden to review interpretations.

At the Amino Acid Laboratory of the Massachusetts General Hospital the fellows observe amino acid and organic acid analyses and learn the biochemical features of metabolic disorders. In addition they observe several enzyme analyses that are specific for certain disorders.

At the New England Newborn Screening Program, fellows observe routine sample preparation of filter paper specimens for newborn screening and the techniques used in screening for over 30 amino acid, organic acid and fatty acid oxidation disorders by tandem mass spectrometry. They also observe enzyme assays for biotinidase deficiency and galactose-1-P uridyltransferase (GALT) for galactosemia. They learn the principles of public health screening, algorithm development, notification, tracking and follow-up abnormal screening tests at the biweekly meetings with program staff and metabolic consultants (Drs. Marsden and Shih) from the HMS Program.

Fellows are evaluated at the completion of each laboratory rotation by the laboratory director. In addition, the Clinical Biochemical Genetics program director meets with fellows on a quarterly basis to discuss overall progress and performance in the program.

Fellows are expected to attend a weekly metabolic clinic during the second year. They review and present results of testing to the families under the supervision of an attending physician.

All fellows attend the weekly course in Advanced Human Genetics during which 12 lectures in topics in biochemical genetics are presented. They must pass an examination given at the end of each series of lectures. Biochemical genetic topics and cases are frequently presented as part of the weekly "Walk Rounds" that follow the lectures.