Background: Hurler syndrome is the most severe form of mucopolysaccharidosis type I. Treatment options include enzymatic replacement therapy ( ERT) and bone marrow /stem cells transplantation. Case report: Female child with dilatated cardiomiopathy diagnosed at one month of age. Coarse features and growth failure suggested MPS I, confirmed at biochemical, enzymatic and molecular level. ERT with laronidase was started at 5 months of age, improving general clinical condition; patient was proposed to transplant. Ductus arteriosus surgery was done for stabilization of pulmonary involvement. and a bacillus Calmette-Guérin lymphadenitis postponed the bone marrow transplantation, successfully performed at the age of 14 months. A cutaneous graft versus host disease was controlled with immunosuppression but at 24 months a severe lung disease brought the doubt of pulmonary graft versus host disease. Despite leukocyte analyses showed non pathological α-L-iduronidase activity after transplant, there was an urinary GAG accumulation when ERT was postponed and so the patient is going on ERT until now. At the age of 36 months heart function and psychomotor development is close to normal, pulmonary symptoms are controlled with inhaled therapy, and she is growing well. Discussion: questions are highlighted concerning biomarkers significance and recommendations to ERT after graft. Mucopolysaccharidosis type I (MPS I) is a rare autossomal recessive lysosomal disease. Here we report a case of a female infant who, at the age of 8 months, was noticed to have hepatomegaly, failure to thrive, development delay and coarse facies. She was referred to our genetic clinics for investigation. At that time, physical examination showed: weight 6425 g, height 64 cm, OFC: 43 cm, mild coarsening of facial features, enlarged tongue, gibbus, hepatomegaly and development delay. The laboratory exams showed evidence of MPS I, with a deficient activity of α-L-iduronidase (0,17 nmol/hr/mg) and two null mutations at the IDUA gene (Hurler (W402X/ W402X), a genotype compatible with Hurler type preditction. The enzyme replacement therapy (ERT) with laronidase was started when she was 16 months old, while she was under evaluation for HSCT (Hematopoietic Stem Cell Transplantation), and stabilized her clinical status and improved respiratory condition. The allogeneic HSCT was performed after she was on ERT for 11 months (the time needed to find a donor), at the age of 27 months . Five months after HSCT the patient shows a very good outcome with leucocyte enzyme activity on the normal range. We emphasize the benefits of ERT before HSCT to stabilize the respiratory symptoms. Two siblings of consanguinous parents were noted to have a neurologic syndrome marked by regression of psychomotor performance from the first year, marked spasticity and progressive central nervous system degeneration (clinical manifestation was like late infantile Metachromatic Leukodystrophy.) Markedly delayed nerve conduction times were evident. Brain MRI showed diffuse white matter lesions without involvement of subcortical U-fibers., activity of arylsulfatase A white blood cells and cultured skin fibroblasts were below 5%. Molecular investigation of ARSA gene showed a homozygote DNA alteration in A905G position in exon 5 which changes amino acide Lys302Arg. The parents were heterozygote for this alteration. Because of some problem with prenatal diagnosis with enzyme assay molecular diagnosis according to sequencing finding was done for this family. Prenatal Diagnosis was done for this family and fetus was heterozygot for this mutation. This child was affected according to enzyme assay after birth. Molecular investigation for multiple sulfatase deficiency and Saposin B deficiency were negative in this family. Thus, we believe these patients may represent a new form of ARSA deficiency. Methods: We report follow-up of 29 French adult patients with stabilized type 1 GD treated with taliglucerase during 6 months. Results: 29 patients (12 females; median age 43.9). 7 were splenectomized, 2 had bleeding and 10 had a history of bone episodes (1 pathological fracture, 5 avascular necrosis & 4 bone infarcts). Previous treatment was discontinued for a few months because of a shortage of imiglucerase. Median posology was 120 U/kg/month. Biological evaluation at inclusion and at 6 months of treatment, median (min-max) was: hemoglobin G/dl: 14.1 (10.8-16.7) /13.9 (11.9-16.4); platelets 103/dl (only in 22 patients without splenectomy): 124 (50-182) /122. 5 (58.0-207.0) ; chitotriosidase: 1519 (110-12500) /1000 (108-11050). No clinical event related to the disease evolution was notified. 6 patients experienced 21 adverse events (AE) among which 2 patients had serious drug-related AEs with treatment discontinuation: severe anaphylactic reaction and chest pain. Conclusion: Taliglucerase seems to be an effective enzyme replacement therapy in 1GD stabilized patients. Potential side effects should be monitored in all patients and, in particular, those who have received previous exogenous ERT treatment. Conflict of Interest declared. Enzyme Replacement Therapy (ERT) for Pompe disease was approved for clinical use in 2006 based on the efficacy of alglucosidase alfa in classic infantile patients. In this ongoing prospective study, we included 71 adults who were treated with 20 mg/kg alglucosidase alfa every other week. Effects of ERT were compared with natural course. The median treatment duration was 23 months (range 5-47 months). Muscle strength increased significantly after start of ERT: 1.4% points/year for manual muscle testing and 4.0% points/year for hand held dynamometry. The calculated difference between natural course and treatment course was 3.3% points/year for manual muscle testing (P<0.001) and 7.9% points/year for hand held dynamometry (P<0.001). During ERT, FVC remained stable in upright position and declined further in supine position but less than before. For FVC in upright position, the calculated difference between natural course and treatment course was 1.75% per year (P=0.08). Favorable prognostic factors for treatment response were female gender for muscle strength and younger age for pulmonary function. Our study shows that ERTsignificantly alters the natural course in adult patients with Pompe disease. Muscle strength increased and pulmonary function in upright position stabilized, while both parameters declined before start of ERT. Conflict of Interest declared. Background: HPP, heritable rickets due to TNSALP gene mutations, may present in infancy with failure to thrive, fractures and respiratory compromise. ENB-0040 (bone-targeted, recombinant TNSALP) treatment is associated with respiratory function and motor development improvements (Greenberg, ASHG 2010) . Primary efficacy, radiographic change in rickets is reported. Objective: Evaluate rickets severity after 6 and 12-mos of ENB-0040 therapy. Design/Methods: 6-mo Ph2 study (with extension phase on-going); patients received 1 iv infusion, then thrice weekly subcutaneous injections (1-3 mg/kg/dose). A Radiographic Global Impression of Change (RGI-C) was developed to assess rickets in HPP. This is a 7-point scale, where −3 represents severe worsening and +3 complete healing of rickets. Rickets Severity Scale (RSS)(Thacher, 2000) is a 10-point scale scoring metaphyseal changes from 0(no evidence of rickets) to 10(severe rickets). Results: 11 patients enrolled. One withdrew and another died of sepsis unrelated to ENB-0040. "Responders" had a mean RGI-C score of>+2. At 6 and 12-mos, 9/10 and 8/9 patients were responders. Mean(±SD) RSS score for 9 patients at baseline was 8.5 (± 2.4) LSD Unit, Royal Free Hospital, London, United Kingdom Introduction: Gaucher disease is an inherited metabolic disorder in which a deficiency of the lysosomal enzyme glucocerebrosidase leads to pathology, primarily within the spleen and bone. Due to a global shortage, from 2009 to mid 2010, of the widely used enzyme replacement therapy (ERT), patients were allowed to be treated with VPRIV. (velaglucerase alfa, Shire Human Genetic Therapies), which was then in the late trial phase. Discussion on patient group: The patients receiving velaglucerase alfa at this time were newly presenting patients requiring ERT. All six patients were naïve to ERT. The subjects ranged in age from 17 to 69 years at start of treatment. Results: Average treatment duration for this group is now 11.5 months. Infusions have been well tolerated. The average dose used for this patient group is 30 units per kilogram two-weekly. The only adverse event reported, fatigue (by 1 patient), was present before ERT. Five subjects have shown improvement in platelet count within the first 10 months. Anaemia, where present (in 2 patients), has resolved. Visceral scans of these subjects and measurement of plasma chitotriosidase revealed a corresponding response. Conclusions: Initial results of velaglucerase alfa treatment in patients, now treated beyond the clinical studies, are encouraging.