cholesterol. It can present with a wide range of neurologic findings. Symptoms can be present since early childhood and late infantile presentations are the classical presentation of the disease. Neverthe- less, more adult patients with NPC have been described, expanding the neurologic spectrum of the disease. Material and Methods: Retrospective study and review of neuroimaging, neurophysiological, biochemical and molecular stud- ies carried out in the course of 45 adult patients with NPC suspicion. Results: 20 patients were referred because of generalized dystonia with progressive cognitive decline/dementia; 15 patients were referred because of cerebellar ataxia with vertical ophtalmoparesis; 4 patients had dystonia without an apparent cognitive decline, but with eye ophtalmoparesis; the other remaining 6 patients had a complex neurological picture with cerebellar syndrome, generalized dystonia, ophtalmoplegia, cognitive decline and pyramidal syn- drome. Eight out of 45 patients were confirmed to have NPC by filipin staining (2 patients required molecular analysis because of “variant filipin pattern”). Regarding clinical presentation, all positive NPC cases had VSGP with typically downward gaze palsy. Two patients had generalized dystonia with dementia; one patient had cerebellar ataxia with typical VGSP but no cognitive decline; one patient had laryngeal dystonia as prominent feature. None of the patients (but one) had previous history of prolonged jaundice; two patients had splenomegaly detected by ultrasound. On MRI, mild cerebellar atrophy with periventricular leukoencephalopathy was found in two patients. Conclusion: Neurological manifestations in NPC patients are extremely variable, even in the same sibship. Better understanding of the natural history of the disease is crucial for evaluation of potential therapeutic approaches in such devastating disorder. doi:10.1016/j.ymgme.2012.11.155 142 “You can't always get what you want”: Filipin staining unmasking lysosomal acid lipase (LAL) deficiency in a young child Charles Lourenco a , Fernanda Timm b , Maira Burin b , Roberto Giugliani b , John Hamilton c , Jennifer Burg d , Wilson MarquesJr. a , a University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil, b Federal University of Rio Grande do Sul, Porto Alegre, Brazil, c Yorkhill Hospital, Glasgow, Scotland, UK, d Synageva BioPharma Corp, Lexington, MA, USA LAL deficiency is a lysosomal storage disease characterized by cholesteryl ester and triglyceride accumulation presenting as a continuum, classically divided into Wolman disease and cholesteryl ester storage disease (CESD). Niemann–Pick disease type C (NPC) is a complex lysosomal disease caused by defective intracellular trans- port of cholesterol leading to unesterified cholesterol storage in the late endosome/lysosome system. Unlike LAL deficiency, NPC cannot be diagnosed by enzyme assay. NPC utilizes filipin staining to flouresce the intralysosomal accumulation of unesterified cholester- ol. This recent case describes a 5-year-old Brazilian boy, born to non- consanguineous parents, who was initially diagnosed with NPC due to the characteristic pattern of intense perinuclear fluorescence; however further evaluation confirmed LAL deficiency. Soon after birth, the patient was noted to have cholestasis. During his first year of life, his cholestasis remitted but a residual degree of hepatomegaly remained. At age 4, he underwent a liver biopsy and the pathologist suspected a lysosomal storage disease. Investigation for Gaucher disease and Niemann–Pick disease types A and B were negative. Given his high levels of chitotriosidase, a skin biopsy for filipin staining was performed and revealed “classical” NPC pattern in his fibroblasts. Molecular genetics analysis of NPC1/2 genes failed to identify mutations. Before performing molecular investigation with MLPA and cDNA analysis, dried blood spot (DBS) enzyme assay for LAL showed decreased activity, compatible with LAL deficiency. To our knowledge, this is the first report of a patient with LAL deficiency with positive filipin staining; suggesting that this cytochemical test could help identify patients with LAL deficiency. doi:10.1016/j.ymgme.2012.11.156 143 High-risk population screening for mucopolysaccharidoses and Pompe disease Zoltan Lukacs, Hamburg University Medical Center, Hamburg, Hamburg, Germany Mucopolysaccharidoses (MPS) are a group of progressive disor- ders which derive from deficiency of lysosomal enzymes involved in the degradation of glycosaminoglycans. Pompe disease is a rare autosomal-recessive disorder which results from a defect in the lysosomal enzyme-glucosidase (GAA). Recently, enzyme analysis in dried blood specimens opened up the possibility of high-risk population screening which may provide a cost-effective alternative to general newborn screening. We analyzed 602 samples from patients with symptoms compatible with MPS I. In total 47 patients (8%) with MPS I were identified. In addition, 28 patients with MPS II (5%) and 23 patients (4%) with MPS VI were found. Using the same DBS sample for DNA analysis, the biochemical diagnosis of MPS was corroborated by mutation data in 88 % of cases. Another 21 samples (4%) showed significantly elevated enzyme activities in DBS which is compatible with mucolipidoses while two samples showed generally low sulfatase activity which is indicative of a multiple sulfatase deficiency. Furthermore, especially, late-onset variants of Pompe disease may show little and unspecific symptoms, like CK elevations or limb girdle muscle dystrophy. We have analyzed 944 samples from patients with such symptoms for GAA activity. Among those, 14 patients have been confirmed with classical Pompe disease. In summary, high-risk population screening provides an excellent means to detect patients with Pompe and MPS disease who remain otherwise undiagnosed. doi:10.1016/j.ymgme.2012.11.157 144 Progression of pulmonary disease and related changes in lung cholesterol metabolism in mice with Niemann–Pick type C1 deficiency Charina M. Ramirez, Benny Liu, Lam Le, Adam M. Lopez, Arthur G. Weinberg, Stephen D. Turley, University of Texas Southwestern Medical School, Dallas, TX, USA Background: Niemann–Pick disease type C1 (NPC1) is character- ized by unesterified cholesterol accumulation in the late endosome/ lysosome compartment in all organs. Most literature on NPC1 disease focuses on neurological and liver manifestations, while pulmonary pathology is often under-recognized. Aim: (1) To track progression of pulmonary disease by measure- ment of multiple parameters of sterol/lipid metabolism in the lungs of NPC1 -/- mice at different ages, and (2) characterize lung histology in this model. Methods: Relative lung weights, rates of cholesterol and fatty acid (FA) synthesis, lung cholesterol, and phospholipid (PL) contents, and Abstracts S62