ß 2007 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 143A:1925–1927 (2007) Research Letter Rapid Deterioration of a Patient With Mucopolysaccharidosis Type I During Interruption of Enzyme Replacement Therapy Grzegorz We ˛grzyn, 1 * Anna Tylki-Szyman ´ ska, 2 Anna Liberek, 3 Ewa Piotrowska, 1 Joanna Jako ´ bkiewicz-Banecka, 4 Jolanta Marucha, 2 Barbara Czartoryska, 5 and Alicja We ˛grzyn 4 1 Department of Molecular Biology, University of Gdan ´sk, Kladki 24, Gdan ´sk, Poland 2 Department of Metabolic Diseases, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland 3 Department of Pediatrics, Children’s Gastroenterology and Oncology, Medical University of Gdan ´sk, Nowe Ogrody 1-6, Gdan ´sk, Poland 4 Laboratory of Molecular Biology (affiliated with the University of Gdan ´sk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Kladki 24, Gdan ´sk, Poland 5 Department of Genetics, Institute of Psychiatry and Neurology, Sobieskiego 9, Warsaw, Poland Received 17 February 2007; Accepted 19 March 2007 How to cite this article: We ˛grzyn G, Tylki-Szyman ´ ska A, Liberek A, Piotrowska E, Jako ´ bkiewicz-Banecka J, Marucha J, Czartoryska B, We ˛grzyn A. 2007. Rapid deterioration of a patient with mucopolysaccharidosis type I during interruption of enzyme replacement therapy. Am J Med Genet Part A 143A:1925 – 1927. To the Editor: Mucopolysaccharidosis type I (MPS I; for review see [Neufeld and Muenzer, 2001]) is the first MPS disorder for which specific therapy has become available. Recombinant human a-L-iduronidase (Aldurazyme 1 , laronidase) is used for intravenous enzyme replacement therapy (ERT). Clinical trials demonstrated safety and efficacy of this treatment [Kakkis et al., 2001; Wraith et al., 2004], which has been confirmed in follow-up studies [Wraith, 2005; Sifuentes et al., 2007]. For example, in addition to enhanced distance covered in a 6-min walk and improvement in pulmonary function, hepatos- plenomegaly decreased, growth rate increased, maximal range of motion of shoulder flexion and elbow extension increased, episodes of sleep apnea decreased, hearing improved, and urinary glycosa- minoglycan (GAG) excretion decreased [Kakkis et al., 2001; Wraith et al., 2004; Wraith, 2005; Sifuentes et al., 2007]. Although efficacy of ERT for MPS I has been demonstrated, the high cost of this treatment (over 100,000 USD per year per a patient of the body weight of 20 kg) causes a potential risk of disconti- nuation or interruption of this treatment. Clinical effects of such an interruption in ERT are largely unknown. Recently, a case of discontinuation of ERT for attenuated MPS I, due to pregnancy, documented rapid deterioration [Anbu et al., 2006]. We report on a case of attenuated MPS I whose laronidase therapy was interrupted for 2 months leading to a similar outcome of deterioration that mostly corrected with reinstitution of therapy. Patient A has coarse facial features, flattened nasal bridge, enlarged tongue and lips, widely spaced and poorly formed teeth, strabismus, short neck, funnel-shaped thorax, lumbar gibbus with kyphosis, umbilical hernia, progressive hepatosplenomegaly, corneal opacities, severe joint stiffness with limita- tion of movement, frequent upper respiratory tract infections, frequent episodes of diarrhea, and obstructive sleep apnea. On echocardiography, prolapse of the anterior mitral cusp with 1st degree mitral insufficiency was evident, and thickened mitral cusps were noted. Hair strands revealed structural abnormalities (Fig. 1), characteristic for MPS I [Kloska et al., 2005]. Patient A was diagnosed enzymaticaly for MPS I at age of 4 years. Two mutations in her IDUA alleles, leading to Q70X and D349 changes in the gene product, were determined. She was classified as MPS I-H/S (Hurler/Scheie syndrome, an intermediate form of MPS I) due to the somatic features described above and normal Grant sponsor: Polish Ministry of Science and Higher Education; Grant number: 2 P05A 103 26. *Correspondence to: Prof. Grzegorz We ˛grzyn, Department of Mole- cular Biology, University of Gdan ´sk, Kladki 24, 80-822 Gdan ´sk, Poland. E-mail: wegrzyn@biotech.univ.gda.pl DOI 10.1002/ajmg.a.31831