Case Report Continued neurocognitive development and prevention of cardiopulmonary complications after successful BMT for I-cell disease: a long-term follow-up report S Grewal 1 , E Shapiro 2 , E Braunlin 3 , L Charnas 4 , W Krivit 1 , P Orchard 1 and C Peters 1 1 Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA; 2 Pediatric Neuropsychology, University of Minnesota, Minneapolis, MN, USA; 3 Pediatric Cardiology, University of Minnesota, Minneapolis, MN, USA; and 4 Pediatric Neurology, University of Minnesota, Minneapolis, MN, USA Summary: I-cell disease or mucolipidosis type II, a rare inherited storage disorder of lysosomal enzyme localization, is characterized by dysostosis multiplex, progressive severe psychomotor retardation and death by 5–8 years from congestive heart failure and recurrent pulmonary infec- tions. A 19-month old girl with I-cell disease received a bone marrow transplant (BMT) from an HLA-identical carrier brother. At the age of 7 years, 5 years after BMT, she has no history of respiratory infections. Her cardiac function remains normal with a shortening fraction of 47%, and she continues to gain neurodevelopmental milestones, albeit at a very slow rate. Musculoskeletal deformities have worsened despite BMT. This is the first report describing neurodevelopmental gains and preven- tion of cardiopulmonary complications in I-cell disease after BMT. Bone Marrow Transplantation (2003) 32, 957–960. doi:10.1038/sj.bmt.1704249 Keywords: hematopoietic cell transplantation; I-cell disease; mucolipidosis II I-cell disease or mucolipidosis II (ML-II) is a rare autosomal recessive disorder resulting from defective intracellular trafficking of lysosomal enzymes in cells of mesenchymal origin. 1,2 Clinical features resemble Hurler’s syndrome with facial dysmorphology, hepatosplenomegaly, progressive cardiac dilatation and dysfunction, hernias, neurocognitive delay, and multiple skeletal deformities (dysostosis multiplex). 1,3 ML-II patients can be differen- tiated clinically from Hurler’s syndrome by an earlier age of onset, prominent gingival hypertrophy, severe psycho- motor (particularly motor) retardation, and absence of mucopolysacchariduria. Physiologically, enzymes normally destined for the lysosomes undergo phosphorylation on position 6 of a mannose residue in a two-step process inside the Golgi apparatus, to synthesize a mannose 6-phosphate recogni- tion marker which allows targeting of the enzyme to the lysosomes. 4 In ML-II, the enzyme GlcNAc phosphotrans- ferase (or phosphotransferase), catalyzing the first-step of phosphorylation, is defective. 2 This results in deficient synthesis of the recognition marker on enzymes destined for the lysosomes and instead leakage of lysosomal enzymes into body fluids and serum. Patients have severe and progressive mental retardation with recurrent respiratory infections; death usually occurs by 5–8 years of age due to cardiorespiratory complications. Diagnosis can be estab- lished by clinical features and biochemically by demon- strating deficiency of the phosphotransferase in leukocytes/ tissues or significantly increased levels of lysosomal enzymes in serum. Hickman and Neufeld, in 1972, 5 showed that I-cell fibroblasts were capable of internalizing lysosomal enzymes secreted by normal cells, but normal cells were unable to take up enzymes secreted by I-cell fibroblasts. This formed our basis for considering allogeneic bone marrow trans- plantation (BMT). This is the first report describing continued intellectual development with prevention of cardiorespiratory complications in a patient with ML-II after BMT. Case report A 12-month-old girl was evaluated in the genetics clinic for progressive facial dysmorphia since birth. There was no prior history of respiratory infections. Physical features included gingival hypertrophy, diastasis rectii, hepatome- galy (5 cm below the costal margin), no cardiac murmurs, and prominent kyphosis. Skeletal survey showed classical radiological features of dysostosis multiplex similar to that seen in Hurler’s syndrome. She was unable to sit or crawl, but had good head control and reached for objects. Leukocyte alpha-l-iduronidase enzyme activity was normal and no mucopolysacchariduria was detected. Further evaluation revealed a low leukocyte GlcNAc phospho- transferase activity (6.5% of control) with increased plasma Received 5 March 2003; accepted 4 May 2003 Correspondence: Dr SS Grewal, Pediatric Blood and Marrow Trans- plantation, University of Minnesota, 420 Delaware St SE, MMC 477, Minneapolis, MN 55455 USA; E-mail: grewa002@umn.edu Bone Marrow Transplantation (2003) 32, 957–960 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt