ARTICLE Long-term speech and language developmental issues among children with Duarte galactosemia Kimberly K. Powell, PhD, Rd1,2, Kim Van Naarden Braun, PhD2, Rani H. Singh, PhD, Rd3, Stuart K. Shapira, MD, PhD4, Richard S. Olney, MD, MPH3,4, and Marshalyn Yeargin-Allsopp, MD2 Purpose: There is limited information on long-term outcomes among approximately 1 in 2000 births, compared with 1 in 47,000 1,2 children with Duarte galactosemia and controversy about treatment of births for classic galactosemia. Infants with this variant form this potentially benign condition. This study examined developmental of galactosemia are compound heterozygotes for the Duarte disabilities and issues that required special education services within a variant mutation and a classic galactosemia mutation. The pres- population-based sample of children with Duarte galactosemia. Methods: ence of the Duarte variant mutation results in a GALT enzyme Children born between 1988 and 2001 who were diagnosed with Duarte level approximately 25% of that of children with normal func- galactosemia and resided in the five-county metropolitan Atlanta area at tioning GALT, compared with almost zero activity among chil- birth and from 3 to 10 years of age were linked to the (1) Metropolitan dren with classic galactosemia. Atlanta Developmental Disabilities Surveillance Program, an ongoing, Untreated classic galactosemia can result in serious medical population-based surveillance system for selected developmental dis- outcomes, including feeding problems, hepatotoxicity, renal abilities and (2) Special Education Database of Metropolitan Atlanta. damage, brain damage, cataracts, sepsis, and death. Treatment Special education records were reviewed for children who linked. can prevent many of the acute complications among infants, but Clinical genetics records were reviewed to assess laboratory levels at clinical studies report poor long-term outcomes even with ex- the time of diagnosis and metabolic control during treatment. Results: cellent treatment, including neurologic dysfunction, speech dis- Of the 59 eligible children, none were found to have intellectual orders, growth delays, ovarian failure, and intellectual disabil- 3,4 disability, cerebral palsy, hearing loss, vision impairment, or an autism ities. spectrum disorder. However, five, 8.5% of 3 to 10 years or 15.2% of Unlike classic galactosemia, Duarte galactosemia has been 5 eligible 8 years, were identified as having received special education considered benign by some clinicians. However, there has been services, four of whom were confirmed with a speech or language controversy about defining this condition as benign, as well as 5–8 disorder, or were receiving services for speech or language or both whether and when to implement dietary interventions. Most compared with 4.5% and 5.9% of children without Duarte galactosemia, previous studies report no clinical abnormalities despite bio- respectively. Conclusions: Despite galactose restriction until 1 year, chemical abnormalities but still make recommendations to ini- select developmental issues associated with special education, specifi- tiate treatment for various elevated levels of galactose-1-phos- cally involving speech and language, have been found among some phate (Gal-1-P). children with Duarte galactosemia. Genet Med 2009:11(12):874–879. Although data on the neurodevelopmental outcomes of children with Duarte galactosemia are limited, the few studies that have Key Words: Duarte galactosemia, developmental disabilities, speech been conducted either have examined intellectual disabilities solely and language disorder, newborn screening, population based and not other developmental outcomes, such as learning disorders or speech and language delays, or have evaluated developmental outcomes in younger ages when standardized cognitive function- hrough newborn screening for galactosemia, Duarte galac- ing tests are less stable than when administered to school-age Ttosemia has been increasingly identified in the population. children.5,6,9,10 This study examined both developmental disabili- The Duarte allele, with a frequency among a panethnic US ties and other developmental outcomes that require special educa- population of approximately 5%, is the most common mutation tion services in childhood among a population-based sample of 1 affecting galactose-1-phosphate uridyl transferase (GALT). children with Duarte galactosemia. Duarte galactosemia is relatively common, with a prevalence of From the 1Association for University Centers on Disabilities (AUCD); MATERIALS AND METHODS 2 Centers for Disease Control and Prevention (CDC), National Center on Study population Birth Defects and Developmental Disabilities (NCBDDD), Developmental Disabilities Branch; 3Division of Medical Genetics, Department of Human The study population included children born during the pe- Genetics, Emory University School of Medicine; and 4CDC, NCBDDD, riod 1988 to 2001 who were diagnosed with Duarte galac- Pediatric Genetics Team, Atlanta, Georgia. tosemia after positive identification through the Georgia New- Kim Van Naarden Braun, PhD, Centers for Disease Control and Prevention, born Screening Program. Children were included in the study National Center on Birth Defects and Developmental Disabilities, 1600 sample if they resided in the five-county metropolitan Atlanta Clifton Road, M/S E-86, Atlanta, GA 30333. E-mail: [email protected]. area (Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties) at The findings and conclusions in this report are those of the authors and do birth and at any point during the period when they were 3 to 10 not necessarily represent the official position of the Centers for Disease years. Residency at birth was based on the mother’s address on Control and Prevention. the newborn screening and birth certificate records. Residency Disclosure: The authors declare no conflict of interest. during the period when children were 3 to 10 years was deter- ® Submitted for publication May 21, 2009. mined using the Accurint search engine based on the mother’s name, address, and any other available information (such as Accepted for publication September 11, 2009. maternal date of birth or social security number). Children were Published online ahead of print November 6, 2009. excluded if they were not followed clinically by the Division of DOI: 10.1097/GIM.0b013e3181c0c38d Medical Genetics at Emory University, in Atlanta, GA. 874 Genetics IN Medicine • Volume 11, Number 12, December 2009 Genetics IN Medicine • Volume 11, Number 12, December 2009 Duarte galactosemia and developmental issues Data sources monitoring system for select developmental disabilities (intel- lectual disability, cerebral palsy, hearing loss, vision impair- Georgia Newborn Screening Program ment, and autism spectrum disorders) conducted by the Devel- The Georgia Newborn Screening Program is a collaborative opmental Disabilities Branch at the Centers for Disease Control effort between the Division of Medical Genetics, Department of and Prevention. MADDSP is based on administrative record Human Genetics at Emory University School of Medicine and review, at multiple sources, including educational, clinical, and the Georgia Department of Human Resources, Division of Pub- service records, to identify children with developmental disabil- lic Health. During the period 1988 to 1990, an abnormal new- ities at 8 years. Specific surveillance methods and case defini- born screening test result for galactosemia was defined as the tions are published elsewhere.13 This study used available data 11 absence of fluorescence on the “Beutler” assay. During the from the 1996, 2000, 2002, and 2004 surveillance years (birth Ͼ period 1991 to 2001, additional criteria of 10 mg/dL of total cohorts 1988, 1992, 1994, and 1996). For children not born in 12 galactose on the “Hill” assay were added. an eligible surveillance year who were found to be receiving Emory clinical genetics records special education services, a special MADDSP review was conducted to determine if these children met the MADDSP case Following an abnormal newborn screen for galactosemia, definition for a developmental disability. children were referred to the Division of Medical Genetics at The Special Education Database of Metropolitan Atlanta Emory University and diagnostic testing was performed by (SEDMA) was created by the Centers for Disease Control and obtaining Gal-1-P and urine galactitol levels, GALT activity, Prevention Developmental Disabilities Branch by merging the and mutation analysis. Children identified with Duarte galac- electronic files from all nine school systems in metropolitan tosemia were treated with a galactose-restricted (primarily by Atlanta to identify children 3 to 10 years who received special lactose restriction) diet until 1 year. Typically, children were education services. SEDMA exceptionalities represent the type seen at 4 to 6 months of age for monitoring before beginning of special education placement (e.g., learning disorder or solids and again at 10 to 12 months of age after a milk challenge speech/language impairment) and not a disability specific diag- unless more frequent monitoring was indicated. If Gal-1-P nosis. Children may not have a specific exceptionality but be levels were within normal limits on a normal diet, the child was eligible to receive related services such as those for speech or no longer monitored by the Emory Clinical Genetics Program language or both. Data were used for the 1996 to 2004 school and was encouraged