Health & Disability

April 21, 2008 • Volume 5, Number 2


Dr. Kimberly Powell is the 2006 AUCD Fellow working as a member of the Developmental Disability Team in the Division of Birth Defects and Developmental Disabilities at the National Center for Birth Defects and Developmental Disabilities (NCBDDD) at CDC. She presented the following study at the AUCD-NCBDDD Fellowship Webinar held on March 26, 2008. Presentation materials and audio file of the webinar have been archived online.

Developmental Disabilities and Inborn Errors of Metabolism -
Updating the Study on the Long-Term Developmental Outcomes of Children with an Inborn Error of Metabolism


In the United States, over 4 million infants are screened each year for inborn errors of metabolism (IEM) as part of state-mandated newborn screening programs. IEM are caused by genetic mutations that interrupt some aspect of a metabolic pathway. Typically, a pathway enzyme, responsible for the breakdown of certain amino, organic or fatty acids, is missing or has lower than normal activity which causes an abnormal buildup of an intermediate metabolite, with associated toxic effects. If untreated, IEM cause metabolic decompensation, behavioral difficulties, poor growth, neurological problems, mental retardation and/or death . However, IEM can be treated through medications and/or strict dietary modifications that limit the offending metabolites and prevent accumulation of toxic intermediates. If treated in early infancy, these symptoms may be reduced or prevented, making them ideal for newborn screening.

While newborn screening has been instrumental in reducing the impact of IEM, the success of a treatment's ability to prevent neurological impairment is dependent on the timeliness of detection and initiation of treatment, patient compliance with treatment protocol and severity/type of IEM. In addition, the number of IEM screened for in newborns is variable by state. Prior to January 1, 2007, Georgia screened for the following IEM: galactosemia, homocystinuria, maple syrup urine disease, phenylketonuria, and tyrosinemia. Disorders that are not detected in the newborn period are usually identified clinically at a later age. A study by Waisbren and colleagues, comparing infants diagnosed by newborn screening versus clinically, found that infants identified through newborn screening had better health outcomes and their parents had a lower stress index rating. Clinically diagnosed infants began treatment a median of 4 months later, experienced 60% more symptoms at time of diagnosis, had more complications after diagnosis, were three times more likely to require additional interventions or special services and were more likely to have significant deficits in communication, daily living skills, socialization and motor skills. Thus, children identified through newborn screening or clinically diagnosed are at risk for developmental disabilities.

The previous study conducted by Van Naarden Braun and colleagues identified three children with mental retardation among the 147 children eligible with a metabolic or endocrine disorder (birth cohorts 1981-1991) and nine children with a developmental disability less severe than mental retardation among the 216 children who screened positive for a metabolic or endocrine disorder (birth cohorts 1981-1995). This study plans to update the work by Van Naarden Braun and colleagues and expand the analysis to include children identified clinically with an IEM in order to examine the magnitude of selected developmental disabilities attributable to IEM in Metropolitan Atlanta.

Specific Aims:
Specific Aim 1: Determine the number of children with an IEM who have a developmental disability or use special education services.

Specific Aim 2: Examine different factors that may play a role in the developmental outcomes of children diagnosed with an IEM such as type of IEM/genotype of IEM , clinical vs. newborn screen identification, age at screen, age at intervention, baseline level of metabolite at treatment initiation, number of hospitalizations, and compliance to treatment.

Study Population:
The study population will include children identified with an IEM (both clinically and via newborn screening) who were born during 1988-2003. Children born from 1988-1996 will be linked to MADDSP data to determine the number children who have an IEM and a developmental disability. Children born from 1989-2003 will be lined to SEDMA data to determine the number of children who have an IEM and use special education services.

Data Sources:
a. Division of Medical Genetics, Department of Pediatrics, Emory School of Medicine
Data on children with an IEM who were born during 1988-2002 and whose mother resided in Metropolitan Atlanta at their birth will be abstracted from medical records at the Division of Medical Genetics of the Emory School of Medicine. Medical information will be reviewed by pediatric geneticists to determine if their developmental disability was attributable to their IEM.

b. Metropolitan Atlanta Developmental Disability Surveillance Program (MADDSP)
Since 1991, the Developmental Disability Branch at the CDC has conducted the Metropolitan Atlanta Developmental Disability Surveillance Program (MADDSP), an ongoing, population-based surveillance system for selected developmental disabilities (mental retardation, cerebral palsy, hearing loss, vision impairment and autism). Data will be used from the 1996, 2000, 2002 and 2004 surveillance years which includes data on 8 year-old children identified with selected developmental disabilities (birth cohorts 1988-1996) who were born and reside in Metropolitan Atlanta (Clayton, Cobb, De Kalb, Fulton and Gwinnett counties).

SEDMA was created by merging the electronic files identifying 3-10 year-old children who receive special education services from all nine public school systems in Metropolitan Atlanta. This includes data on the primary and often secondary Individualized Education Program eligibility categories. School years from 1999-2006 will be used which correspond to 1989-2003 birth cohort.

Data Analysis:
Data on children diagnosed with an IEM will be linked to MADDSP and SEDMA data to determine the number of children with an IEM who have a developmental disability or use special education services. Factors that may have contributed to the developmental outcomes such as newborn versus clinical identification will be summarized. Additionally, the number of children expected to have mental retardation will be calculated using annual and cumulative incidence rates from each disorder screened for in Georgia and the number of live-births for the corresponding area of Metropolitan Atlanta.

Next Steps:
Dr. Powell is the process of finishing the review of off-MADDSP surveillance year cases, confirming residency during study ages in metropolitan Atlanta to be eligible for data linkages, and preparing the manuscript for publication. Future publication pertaining to Dr. Powell's project will be highlighted in upcoming issues of Health and Disability Digest.