Medical Biochemical Genetics Fellowship
Departmental Programs

Seattle Children’s Hospital Biochemical Genetics Clinic

Biochemical genetics involves diagnosing and treating metabolic diseases. These are problems with how the body makes, breaks down or uses proteins, fats or carbohydrates. They are caused by genes that are not normal and cannot make the enzymes the body needs. (Enzymes are found in the blood, organs, saliva and other parts of the body. They are important to all bodily functions.)

These diseases are called inborn errors of metabolism. Our team helps to diagnose, monitor and manage these diseases. We work closely with doctors in other departments at Seattle Children’s and in our Genetics Lab. Most of our patients have complex health problems. They need coordinated, long-term care from a team of experts, like ours.

Diagnosing and treating metabolic diseases early can improve a child’s quality of life. The Washington State Department of Health screens newborns for these diseases. We work with them to provide any follow-up genetic testing and care that newborns need.

Our program is part of the American Board of Medical Genetics–certified training program at the University of Washington. Another name for this area of genetics is metabolic genetics.


Phenylketonuria (PKU) Program at UW

The Cristine M. Trahms Program for Phenylketonuria at the University of Washington is made up of a team of experienced health care professionals. Together, this team provides services to people with PKU and their families in the state of Washington. The program is primarily funded by the Washington State Newborn Screening Program. The State Genetics Program provides families with subsidized formula (paid for by their medical insurance). The programs are closely coordinated to ensure follow-up and appropriate management of individuals with PKU. The PKU program provides multidisciplinary care for patients and families inherited with the PKU disorder. The clinic offers an all-encompassing approach to care providing medical and nutritional assessments as well as nutrition education and developmental testing for all children in the PKU clinic. Our goal is to provide individualized care to each family with our goal of family support and nutritional education to be built into each clinic visit and beyond.


The Urea Cycle Disorders (UCD) Program at SCH

The UCD Program provides multidisciplinary care including consultation, examination, testing, diagnosis, treatment, and genetic counseling for patients with urea cycle disorders and their families. Our goal is to provide patients and families with a comprehensive medical home that is centered on the patient and family. Our mission is to provide each patient with the knowledge, ability, and proper tools to allow them to manage their disorder. The biochemical genetics team is the core within a larger program dedicated to the management of these diseases and providing care by UWMC and SCH specialists in many areas of medicine including psychology, neurodevelopment, neurology, gastroenterology, and organ transplant. The clinic team follows a large group of children and adult patients across the spectrum of UCDs. Our group also works with local hospitals to coordinate the treatment of care during acute emergencies and in routine follow-up closer to each patient's home.


We are active members of the Urea Cycle Disorders Consortium Longitudinal study, sponsored by the Rare Disease Clinical Research Network at the NIH along with the National Urea Cycle Disorders Foundation in order further improve treatment, quality of life, and our understanding of UCDs and to implement newborn screening for all UCDs – including ornithine transcarbamylase deficiency. We are also actively involved in multiple collaborations with urea cycle disorder support groups and with clinical research trials developing novel treatments of UCDs.


Newborn Screening Program

Since Washington State’s Newborn Screening Program began in 1963 with PKU, the Biochemical

Genetics Program has been providing confirmatory diagnostic testing, clinical treatment and care coordination for babies identified with metabolic diseases from infancy to adulthood. The Biochemical and Molecular Genetics Laboratory staff works very hard to prioritize and analyze these samples as quickly as possible. Currently Washington State is screening for 6 amino acid disorders, 5 fatty acid oxidation disorders, 7 organic acid disorders, and 10 other congenital disorders. Details of each disorder can be found at

The Washington State Department of Health (DOH) continues to provide the Newborn Screening confirmation & follow-up program possible with contract funding for the consultative services and additional testing required to confirm or rule out presumptive diagnoses. This confirmatory diagnosis allows for the earliest possible treatment to begin, giving these children the best quality of life and in some cases a normal or nearly normal lifestyle that would not have been possible without this early care. DOH also continues to provide contract funding for metabolic dietitian services for the Newborn Screening Follow-up Program, as well as for outreach services for semi-annual outreach at the Biochemical Genetics Clinics in Spokane.We continue to be actively involved with the Western States Genetic Services Collaborative to study the outcomes of infants with abnormal newborns screens and, in particular, the long-term outcomes of infants identified with Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency.




The Lysosomal Storage Disease (LSD) Program at UW/SCH

The LSD program provides multidisciplinary care including consultation, examination, testing/ diagnosis, treatment, monitoring, and genetic counseling for patients with lysosomal storage diseases and their families. The patients' medical home is centered with the Biochemical Genetics team. The program is dedicated to the management of these rare diseases and provides care by UWMC and SCH specialists in many areas of medicine including ophthalmology, orthopedics, cardiology, neurology, nephrology, pulmonary, otolaryngology, neurodevelopmental, radiology and anesthesia. Our group also works with local hospitals to facilitate transition of treatment to centers closer to each patient's home or for infusions to be done in the patient’s home. Long-term follow-up of patients with these rare diseases is essential.


Patient education and support meetings are held periodically, providing patients and their families an opportunity to mingle with other families and hear about recent advances in the field. There is much ongoing research in the field of lysosomal storage disorders. The UWMC and SCH teams currently have active patient registries for MPS I, MPS II, MPS IV, MPS VI, Pompe disease, Fabry disease, and Gaucher disease. The clinic team follows a large cohort of patients across the spectrum of LSDs as illustrated in Table 2 and long term follow-up of patients with these rare diseases is essential as is continuing to keep abreast of new developments in therapies and care. A clinical trial for Hunter syndrome is in progress at SCH under IRB approval to evaluate long term safety and clinical outcomes of intrathecal Idursulfase enzyme replacement. Another clinical trial on patients with Pompe disease to evaluate the efficacy and safety of alglucosidase alfa produced at the 4000L scale was successful and the medication was approved by the FDA.



Biochemical Genetics Laboratory

The Biochemical Genetics Laboratories (SCH) are led by Dr. Sihoun Hahn and Dr. Rhona Jack. The Biochemical and Molecular Genetics Laboratories serve as a key component of the Biochemical Genetics Program. The laboratories provide rapid, comprehensive diagnostic and monitoring results along with guidance for follow-up. Our laboratory is committed to high quality results. To ensure accuracy, the laboratory is participating in a variety of external proficiency testing programs offered by various national and international agencies (ERNDIM; European network, CAP;College of American Pathologists, CDC; Center for Disease Control).


Research and Development (R & D) Laboratory

The Biochemical Genetics program’s CLIA-certified R&D Laboratory is located at the Seattle Children’s Research Institute (SCRI): Center for Integrative Brain Research (Center Director. Dr. Jan-Marino Ramirez). The facility is fully equipped with a LCMS/ MS and an Illumina Genome Analyzer IIx. Since 2007, the R&D team has continuously focused their efforts on refining current methodologies and developing new tests, with a fundamental goal to improve clinical practice through the implementation and integration of routine laboratory testing. In particular, the lab aims to develop and validate clinical tests to diagnose various metabolic and genetic disorders by utilizing tandem mass spectrometry.


The R&D team has a long-standing interest in developing a mass spectrometry based assay for diseases characterized by the absence and/or reduction of protein markers. We use a highly sensitive and targeted analytical technology, selected reaction monitoring mass spectrometry (SRM-MS), to measure peptides of our interest, which enables efficient translation of protein markers into clinical use as screening and diagnostic tests. As proof-of-concept, we previously demonstrated that SRM-MS analysis of signature peptides can correctly identify patients lacking specific protein markers of three lifethreatening Primary Immunodeficiency Disorders (Proteomics Clin Appl, 2012, R21AI85488). Our efforts (R56AI106784, R21HD069890, and CRFS- 2015-004) to improve the sensitivity of our assay by combining SRM-MS with antibody-based enrichment of target peptides (immuno-SRM) showed that the method can detect extremely low abundance marker proteins of congenital disorders such asCD3e (for SCID), BTK (for XLA), WASP (for WAS), CTNS (for Cystinosis), and ATP7B (for Wilson disease) in dried blood spots. In 2016, we published the proof-of-concept study demonstrating that the immuno-SRM assay readily distinguishes affected cases of Wilson disease from normal controls (p<0.0001) (Journal of proteome research, 2016). We also received an NIH grant (R01AI123135) to further study and develop a multiplexed immuno-SRM assay for screening11different primary immunodeficiency disorders. We believe that our proteomics based approach will provide an efficient and inexpensive screening for a

broad range of genetic disorders. At the heart of translational research, the R&D Laboratory’s goal is to bridge basic research and the clinical applications of novel tests developed for effective patient diagnosis and treatment. Current staffs of the R&D team include Sunhee Jung, PhD and Remwilyn Dayuha, BS which is led by Dr.Sihoun Hahn.