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Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy.
Orphanet J Rare Dis 2018; 13(1):32OJ

Abstract

BACKGROUND

Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants.

METHODS

A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months).

RESULTS

Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients.

CONCLUSIONS

These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

Authors+Show Affiliations

Pediatric Rare Diseases Unit, Department of Pediatrics, MBBM Foundation, ATS Monza e Brianza, Via Pergolesi 33, 20900, Monza, Italy. rossella.parini@unimib.it.Centre of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.Centre for Rare Diseases, University Hospital Santa Maria della Misericordia, Udine, Italy.Department for Women and Children's Health, U.O.C. Inborn Metabolic Diseases, University Hospital, Padova, Italy.Department of Pediatrics, University of Bologna, Bologna, Italy.Department of Pediatrics, University Magna Graecia, Catanzaro, Italy.Department of Pediatrics, University Magna Graecia, Catanzaro, Italy.Department of Translational Sciences, Pediatrics, University Federico II, Naples, Italy.Division of Metabolism Bambino Gesù Children's Hospital, Rome, Italy.Department of Pediatrics, Meyer Children's Hospital, Metabolic and Muscular Unit, University of Firenze, Florence, Italy.Department of Clinical and Experimental Medicine, Metabolic Diseases, Pediatric Clinic, University of Catania, Catania, Italy.Pediatric Rare Diseases Unit, Department of Pediatrics, MBBM Foundation, ATS Monza e Brianza, Via Pergolesi 33, 20900, Monza, Italy.Department of Pathophysiology and Transplantation, Pediatric Highly Intensive Care Unit, University of Milano, IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Milan, Italy.Department of Pediatrics, University of Torino, Torino, Italy.Department of Pediatrics, Meyer Children's Hospital, Metabolic and Muscular Unit, University of Firenze, Florence, Italy.Department of Pediatrics, University of Torino, Torino, Italy.Division of Metabolism Bambino Gesù Children's Hospital, Rome, Italy.Centre of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.Rare Diseases Unit, Pediatric Hospital Istituto Giannina Gaslini, Genoa, Italy.Centre for Rare Diseases, University Hospital Santa Maria della Misericordia, Udine, Italy.

Pub Type(s)

Journal Article
Multicenter Study
Observational Study

Language

eng

PubMed ID

29422078

Citation

Parini, Rossella, et al. "Long Term Clinical History of an Italian Cohort of Infantile Onset Pompe Disease Treated With Enzyme Replacement Therapy." Orphanet Journal of Rare Diseases, vol. 13, no. 1, 2018, p. 32.
Parini R, De Lorenzo P, Dardis A, et al. Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. Orphanet J Rare Dis. 2018;13(1):32.
Parini, R., De Lorenzo, P., Dardis, A., Burlina, A., Cassio, A., Cavarzere, P., ... Bembi, B. (2018). Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. Orphanet Journal of Rare Diseases, 13(1), p. 32. doi:10.1186/s13023-018-0771-0.
Parini R, et al. Long Term Clinical History of an Italian Cohort of Infantile Onset Pompe Disease Treated With Enzyme Replacement Therapy. Orphanet J Rare Dis. 2018 02 8;13(1):32. PubMed PMID: 29422078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. AU - Parini,Rossella, AU - De Lorenzo,Paola, AU - Dardis,Andrea, AU - Burlina,Alberto, AU - Cassio,Alessandra, AU - Cavarzere,Paolo, AU - Concolino,Daniela, AU - Della Casa,Roberto, AU - Deodato,Federica, AU - Donati,Maria Alice, AU - Fiumara,Agata, AU - Gasperini,Serena, AU - Menni,Francesca, AU - Pagliardini,Veronica, AU - Sacchini,Michele, AU - Spada,Marco, AU - Taurisano,Roberta, AU - Valsecchi,Maria Grazia, AU - Di Rocco,Maja, AU - Bembi,Bruno, Y1 - 2018/02/08/ PY - 2017/10/30/received PY - 2018/01/25/accepted PY - 2018/2/10/entrez PY - 2018/2/10/pubmed PY - 2019/3/15/medline KW - Alglucosidase alpha KW - ERT KW - Infantile onset Pompe disease KW - Recombinant human GAA KW - rhGAA SP - 32 EP - 32 JF - Orphanet journal of rare diseases JO - Orphanet J Rare Dis VL - 13 IS - 1 N2 - BACKGROUND: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. METHODS: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). RESULTS: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. CONCLUSIONS: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches. SN - 1750-1172 UR - https://www.unboundmedicine.com/medline/citation/29422078/Long_term_clinical_history_of_an_Italian_cohort_of_infantile_onset_Pompe_disease_treated_with_enzyme_replacement_therapy_ L2 - https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0771-0 DB - PRIME DP - Unbound Medicine ER -