JNS-13741; No of Pages 2 Journal of the Neurological Sciences xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy Keywords: Pompe disease Late-onset Pompe disease Gastrointestinal symptoms Enzyme replacement therapy
Dear Sirs, Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid alpha glycosidase (GAA) due to mutations in the GAA gene. The main clinical and prognostic features in late-onset Pompe disease (LOPD) are proximal and axial pareses in the limb girdles and respiratory insufficiency due to glycogen storage in the skeletal muscles [1]. Lower gastrointestinal (GI) symptoms have been sparsely reported in these patients [2–4], although lysosomal accumulation of glycogen in intestinal smooth muscle has been shown in autopsies [5,6]. We report herein a patient with LOPD who presented relevant lower GI symptoms that abated soon after enzyme replacement therapy (ERT) was started. We intend to raise awareness of the occurrence of these GI symptoms in LOPD patients while describing the response of one such patient to ERT. A 64 year-old Caucasian male was referred to the Neurology Department presenting with progressive limb-girdle muscular weakness for the past 30 years. Five years after the initial symptoms, he presented with respiratory insufficiency requiring non-invasive ventilation at the time, and mechanical ventilation ten years later. Three muscular biopsies had been performed showing just mild, nonspecific myopathic changes. At referral, he was non-ambulatory and showed severe muscle weakness in extensor muscles of head and neck, proximal weakness and amyotrophy of scapular and pelvic girdles, and patellar and Achilles areflexia. EMG data were compatible with a myopathic disorder affecting mainly proximal muscles of the upper and lower limbs. CK was slightly increased at 232 IU/L. A DBS test was performed showing low GAA enzymatic activity, and Pompe disease was confirmed in lymphocytes and by genetic analysis (heteroallelic for IVS1-13T N G and P-Asp282His mutations). About the time the patient was diagnosed with Pompe, he started showing lower GI symptoms (chronic constipation, bloating, abdominal pain, occasional diarrhea and episodes of intestinal sub-occlusion), which required treatment with octreotide. Twelve months later, the patient started receiving ERT and after four months, the gastrointestinal symptoms disappeared and octreotide
could be discontinued. One year after ERT initiation, the patient was able to walk, aided by a walker, about 30 m but no improvement was observed in respiratory function. The GI symptoms usually reported by Pompe patients and thus, included in treatment guidelines, are upper GI symptoms, such as swallowing difficulties [1]. Lower GI symptoms, including diarrhea and constipation, have been sparsely reported [2–4], although their presence has been disclosed as more common in a recent survey [7]. Marked improvement or complete resolution of these symptoms was observed after 3 to 12 months of ERT in the majority of patients in previous reports [2–4], and after four months in our patient. Although prospective studies in large number of patients should be conducted to confirm this treatment effect, evidence starts summing up suggesting the early response of all sorts of GI symptoms to ERT. Ethical standard On behalf of all the authors, the corresponding author states that we acted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this case report. Conflicts of interest The authors declare that they have no conflict of interest. Acknowledgments Almudena Pardo provided translation assistance. References [1] Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, et al. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve Mar 2012; 45(3):319–33. [2] Bernstein DL, Bialer MG, Mehta L, Desnick RJ. Pompe disease: dramatic improvement in gastrointestinal function following enzyme replacement therapy. A report of three later-onset patients. Mol Genet Metab Oct–Nov 2010;101(2-3):130–3. [3] Sacconi S, Bocquet JD, Chanalet S, Tanant V, Salviati L, Desnuelle C, et al. Abnormalities of cerebral arteries are frequent in patients with late-onset Pompe disease. J Neurol Oct 2010;257(10):1730–3. [4] Remiche G, Herbaut AG, Ronchi D, Lamperti C, Magri F, Moggio M, et al. Incontinence in late-onset Pompe disease: an underdiagnosed treatable condition. Eur Neurol 2012;68(2):75–8. [5] van der Walt JD, Swash M, Leake J, Cox EL. The pattern of involvement of adult-onset acid maltase deficiency at autopsy. Muscle Nerve Mar–Apr 1987;10(3):272–81. [6] Hobson-Webb LD, Proia AD, Thurberg BL, Banugaria S, Prater SN, Kishnani PS, et al. Autopsy findings in late-onset Pompe disease: a case report and systematic review of the literature. Mol Genet Metab Aug 2012;106(4):462–9. [7] Karabul N, Skudlarek A, Berndt J, Kornblum C, Kley RA, Wenninger S, et al. Urge incontinence and gastrointestinal symptoms in adult patients with Pompe disease: a crosssectional survey. JIMD Rep Aug 26 2014;17:53–61.
http://dx.doi.org/10.1016/j.jns.2015.04.012 0022-510X/© 2015 Elsevier B.V. All rights reserved.
Please cite this article as: Pardo J, et al, Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy, J Neurol Sci (2015), http://dx.doi.org/10.1016/j.jns.2015.04.012
2
Letter to the Editor
Julio Pardo⁎ Tania García-Sobrino Ana López-Ferreiro Department of Neurology, Hospital Clínico, Santiago de Compostela (A Coruña), Spain ⁎Corresponding author. Tel.: +34 981950332. E-mail addresses: [email protected] (J. Pardo), [email protected] (T. García-Sobrino), [email protected] (A. López-Ferreiro). 10 February 2015 Available online xxxx
Please cite this article as: Pardo J, et al, Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy, J Neurol Sci (2015), http://dx.doi.org/10.1016/j.jns.2015.04.012
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy Keywords: Pompe disease Late-onset Pompe disease Gastrointestinal symptoms Enzyme replacement therapy
Dear Sirs, Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid alpha glycosidase (GAA) due to mutations in the GAA gene. The main clinical and prognostic features in late-onset Pompe disease (LOPD) are proximal and axial pareses in the limb girdles and respiratory insufficiency due to glycogen storage in the skeletal muscles [1]. Lower gastrointestinal (GI) symptoms have been sparsely reported in these patients [2–4], although lysosomal accumulation of glycogen in intestinal smooth muscle has been shown in autopsies [5,6]. We report herein a patient with LOPD who presented relevant lower GI symptoms that abated soon after enzyme replacement therapy (ERT) was started. We intend to raise awareness of the occurrence of these GI symptoms in LOPD patients while describing the response of one such patient to ERT. A 64 year-old Caucasian male was referred to the Neurology Department presenting with progressive limb-girdle muscular weakness for the past 30 years. Five years after the initial symptoms, he presented with respiratory insufficiency requiring non-invasive ventilation at the time, and mechanical ventilation ten years later. Three muscular biopsies had been performed showing just mild, nonspecific myopathic changes. At referral, he was non-ambulatory and showed severe muscle weakness in extensor muscles of head and neck, proximal weakness and amyotrophy of scapular and pelvic girdles, and patellar and Achilles areflexia. EMG data were compatible with a myopathic disorder affecting mainly proximal muscles of the upper and lower limbs. CK was slightly increased at 232 IU/L. A DBS test was performed showing low GAA enzymatic activity, and Pompe disease was confirmed in lymphocytes and by genetic analysis (heteroallelic for IVS1-13T N G and P-Asp282His mutations). About the time the patient was diagnosed with Pompe, he started showing lower GI symptoms (chronic constipation, bloating, abdominal pain, occasional diarrhea and episodes of intestinal sub-occlusion), which required treatment with octreotide. Twelve months later, the patient started receiving ERT and after four months, the gastrointestinal symptoms disappeared and octreotide
could be discontinued. One year after ERT initiation, the patient was able to walk, aided by a walker, about 30 m but no improvement was observed in respiratory function. The GI symptoms usually reported by Pompe patients and thus, included in treatment guidelines, are upper GI symptoms, such as swallowing difficulties [1]. Lower GI symptoms, including diarrhea and constipation, have been sparsely reported [2–4], although their presence has been disclosed as more common in a recent survey [7]. Marked improvement or complete resolution of these symptoms was observed after 3 to 12 months of ERT in the majority of patients in previous reports [2–4], and after four months in our patient. Although prospective studies in large number of patients should be conducted to confirm this treatment effect, evidence starts summing up suggesting the early response of all sorts of GI symptoms to ERT. Ethical standard On behalf of all the authors, the corresponding author states that we acted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this case report. Conflicts of interest The authors declare that they have no conflict of interest. Acknowledgments Almudena Pardo provided translation assistance. References [1] Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, et al. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve Mar 2012; 45(3):319–33. [2] Bernstein DL, Bialer MG, Mehta L, Desnick RJ. Pompe disease: dramatic improvement in gastrointestinal function following enzyme replacement therapy. A report of three later-onset patients. Mol Genet Metab Oct–Nov 2010;101(2-3):130–3. [3] Sacconi S, Bocquet JD, Chanalet S, Tanant V, Salviati L, Desnuelle C, et al. Abnormalities of cerebral arteries are frequent in patients with late-onset Pompe disease. J Neurol Oct 2010;257(10):1730–3. [4] Remiche G, Herbaut AG, Ronchi D, Lamperti C, Magri F, Moggio M, et al. Incontinence in late-onset Pompe disease: an underdiagnosed treatable condition. Eur Neurol 2012;68(2):75–8. [5] van der Walt JD, Swash M, Leake J, Cox EL. The pattern of involvement of adult-onset acid maltase deficiency at autopsy. Muscle Nerve Mar–Apr 1987;10(3):272–81. [6] Hobson-Webb LD, Proia AD, Thurberg BL, Banugaria S, Prater SN, Kishnani PS, et al. Autopsy findings in late-onset Pompe disease: a case report and systematic review of the literature. Mol Genet Metab Aug 2012;106(4):462–9. [7] Karabul N, Skudlarek A, Berndt J, Kornblum C, Kley RA, Wenninger S, et al. Urge incontinence and gastrointestinal symptoms in adult patients with Pompe disease: a crosssectional survey. JIMD Rep Aug 26 2014;17:53–61.
http://dx.doi.org/10.1016/j.jns.2015.04.012 0022-510X/© 2015 Elsevier B.V. All rights reserved.
Please cite this article as: Pardo J, et al, Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy, J Neurol Sci (2015), http://dx.doi.org/10.1016/j.jns.2015.04.012
2
Letter to the Editor
Julio Pardo⁎ Tania García-Sobrino Ana López-Ferreiro Department of Neurology, Hospital Clínico, Santiago de Compostela (A Coruña), Spain ⁎Corresponding author. Tel.: +34 981950332. E-mail addresses: [email protected] (J. Pardo), [email protected] (T. García-Sobrino), [email protected] (A. López-Ferreiro). 10 February 2015 Available online xxxx
Please cite this article as: Pardo J, et al, Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy, J Neurol Sci (2015), http://dx.doi.org/10.1016/j.jns.2015.04.012
