Medical Comorbidities in Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease)

s for the Lysosomal Disease Network's WORLD Symposium Medical Comorbidities in Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease) Heather Adams a, , Erika Augustine , Samantha Potter , Jennifer Kwon , Fred Marshall , Nicole Newhouse , Amy Vierhile , Jonathan Mink , University of Rochester Medical Center, Rochester, NY, USA, Syracuse University, Syracuse, USA Juvenile neuronal ceroid lipofuscinosis (JNCL) is a childhoodonset neurodegenerative, lysosomal storage disease. JNCL causes vision loss, seizures, motor and mental decline, and premature death. Although neurological and psychiatric aspects of JNCL are wellcharacterized, little is known about systemic medical comorbidities. The University of Rochester Batten Center therefore reviewed medical history of 45 males and 41 females with genetically confirmed JNCL who had completed the Unified Batten Disease Rating Scale (UBDRS). Participants’ mean age was 15.1 years old (SD=5.2 years). Excluding neurologic and psychiatric symptoms, the five most commonly parent-reported medical comorbidities were constipation (N=23), incontinence (N=23), acne (N=18), ear infection (N=17), eczema or dry/itchy skin (N=14), and pain (N=13). Fourteen children were reported to have medication allergies. On average, children experienced approximately 4 comorbid health problems (M=3.9, SD=3.0; range=0 to 7). The total number of medical problems (“medical burden”) was positively correlated with age (r=.42, p< .01), psychosocial quality of life (r=.35, p<.05) and with clinician's global impressions of cognitive (r=.35, p<.05) and motor (r=.36, p<.05) function. Although comorbid health problems have not been a focus in the study of children with juvenile Batten disease, they are common and may provide a broader understanding of disease phenomenology and course. doi:10.1016/j.ymgme.2011.11.009 Evaluation of GLB1 In a Novel Ovine Model of GM1-Gangliosidosis Amelia Ahern-Rindell, Masis Isikbay, Bethany McInturff, Megan Supinski, University of Portland, Portland, Oregon, USA A unique form of the lysosomal storage disorder GM1gangliosidosis (GM1) has been identified in sheep. While traditionally GM1 is associatedwith decreased levels of the lysosomal enzyme s-galactosidase (s-gal), this ovine model also has an apparent secondary deficiency of alpha-neuraminidase (neur). Both of these hydrolases are components of a lysosomal multienzyme complex (LMC) whose formation is required to protect these enzymes and prevent their premature degradation within the lysosome. Other sheep have been identified with the traditional form of GM1 leading us to believe that the dual enzyme deficient sheep are unique. Previous work on this model suggests a structurally altered s-gal is produced thus, we hypothesize that this abnormal s-gal interferes with LMC formation leading to the secondary deficiency of neur. We are currently using the evolutionarily related bovine GLB1 gene to create PCR primers to amplify and then sequence the orthologous gene in affected sheep. The majority of mutations identified in the different types of human GM1 patients result in amino acid substitutions, although a few splice site mutations have been reported. To date, no nucleotide base differences were found between normal and GM1-affected sheep exon sequence. However, sequencing efforts continue on a few remaining exons and, we recently initiated investigation of the intron-exon sequence boundaries. Identification of the mutation responsible for these GM1affected sheep should further understanding of this unique animal model while shedding light on the structure of the s-gal protein, the LMC, and hopefully one day, lead to a treatment for this fatal, neurological disorder. doi:10.1016/j.ymgme.2011.11.010 Medical Outcomes and Adaptive Functions in Severe and Attenuated MPS I Alia Ahmed, Taylor Zuck, Kathleen Delaney, Brianna Yund, Chester Whitley, Elsa Shapiro, University of Minnesota, Minneapolis, MN, USA Mucopolysaccharidosis type I (MPS I) is a multi-organ system disease. Hearing difficulties, corneal clouding, skeletal abnormalities, cardio pulmonary problems, CNS problems such as hydrocephalus and sometimes cervical cord compression impede functionality on a day to day basis. Hematopoietic cell transplant (HCT) in the severe Hurler syndrome group is known to ameliorate some of these problems. Similarly, enzyme replacement therapy (ERT) for the attenuated Hurler-Scheie and Scheie syndrome patients increases range of motion, decreases hepatosplenomegaly, but other benefits are not clear. Methods: To test our hypothesis that these two treatments have differing medical and functional outcomes, we compared the baseline medical history and adaptive behavior functioning (Vineland Adaptive Behavioral Scales) for two groups of patients over 6 years of age, N=18 children who are post transplant for Hurler syndrome and N=14 children who have had ERT for attenuated MPS I. We also examined years since the onset of both treatments as a covariate. Results: In 14 patients who had ERT, 13 have corneal clouding, 10 have hearing difficulties, 13 have hepatosplenomegaly, 3 have hydrocephalus with shunt placement and all have skeletal abnormalities and valvular diseases. In 18 patients who had HCT, 15 have corneal clouding, 12 have hearing difficulties, 10 have hepatosplenomegaly, 2 have hydrocephalus and all have skeletal abnormalities and