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Wiener klinische Wochenschrift

, Volume 126, Issue 3–4, pp 133–137 | Cite as

Effects of immune modulation therapy in the first Croatian infant diagnosed with Pompe disease: a 3-year follow-up study

  • Josko MarkicEmail author
  • Branka Polic
  • Luka Stricevic
  • Vitomir Metlicic
  • Radenka Kuzmanic-Samija
  • Tanja Kovacevic
  • Ivana Erceg Ivkosic
  • Julije Mestrovic
case report

Summary

Pompe disease is a storage disorder characterized by deficient or absent activity of the enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen accumulates in muscle tissues. Patients with a classic infantile-onset form present by the first few months of life with hypertrophic cardiomyopathy and muscle weakness. If left untreated, these patients rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alpha antibody titers. However, CRIM-positive patients also sometimes develop robust antibody titers. High antibody titers complicate therapeutic management, and those patients have a worse clinical outcome of enzyme replacement therapy (ERT).

Four years ago, we successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom ERT had to be discontinued because of severe infusion-associated reactions. She was found to be positive for anti-alglucosidase alpha antibodies. IMT (rituximab, methotrexate, and intravenous gammaglobulin) was started, and ERT was safely reintroduced during the IMT induction phase without any complications. Antibodies disappeared; IMT was tapered and discontinued; and cardiomyopathy steadily improved. During more than 3 years of follow-up, she remained ventilator dependent, and no gains in motor skills were noticed. The antibodies are still undetectable, and no adverse reactions associated with IMT had occurred. The cardiomyopathy is gradually increasing, but there is still ~ 50 % reduction as compared with the highest value measured. Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant cannot be solely attributed to IMT, this protocol proved itself efficient and safe.

Keywords

Glycogen storage disease type II Infantile Immunomodulation Rituximab Cardiomyopathy 

Wirkung einer immunmodulatorischen Therapie beim ersten kroatischen Kind mit der Diagnose einer Pompe’schen Krankheit: eine Verlaufsstudie über 3 Jahre

Zusammenfassung

Die Pompe’sche Krankheit ist eine Speicherkrankheit, die durch eine gestörte oder fehlende Aktivität des Enzyms saure alpha-Glucosidase gekennzeichnet ist. Als Folge des ineffizienten Stoffwechsels reichert sich Glykogen im Muskelgewebe an. Patienten mit der klassischen Form des Ausbruchs der Erkrankung im Kindesalter präsentieren sich bereits in den ersten Lebensmonaten mit einer hypertrophen Kardiomyopathie und Muskelschwäche. Unbehandelt sterben diese Patienten rasch am kardiorespiratorischen Versagen.

Ein kreuzreaktiv immunologisches Material (CRIM) negativer Status sagt hohe anti-alpha Glucosidase Antikörper voraus. CRIM positive Patienten haben allerdings auch manchmal deutlich erhöhte Antikörper Titer. Hohe Antikörper Titer machen das therapeutische Management kompliziert: diese Patienten sprechen klinisch schlechter auf eine Enzymersatz Therapie an.

Vor 4 Jahren verwendeten wir ein Protokoll einer immumodulatorischen Therapie (IMT) erfolgreich bei einer CRIM positiven Patientin mit Ausbruch der Pompe’schen Krankheit im Kindesalter, bei der die Enzymersatz-Therapie wegen schwerer infusions-assoziierter Reaktionen abgesetzt werden musste. Sie hatte anti-alpha Glucosidase Antikörper. Eine IMT bestehend aus Rituximab, Methotrexat, und intravenösem Gammaglobulin wurde begonnen. Während der IMT konnte die Enzymersatz Therapie wieder sicher ohne irgendwelche Komplikationen begonnen werden. Die Antikörper verschwanden und die IMT konnte ausgeschlichen beziehungsweise abgesetzt werden. Die Kardiomyopathie wurde kontinuierlich besser.

Während mehr als 3 Jahren follow-up blieb die Patientin Respirator abhängig – es wurde keine Besserung der motorischen Fähigkeiten beobachtet. Die Antikörper sind weiterhin unter dem Detektionslimit. Die Kardiomyopathie wird nun langsam schlechter – ist aber noch immer 50 % besser im Vergleich zum schlechtesten im Verlauf gemessenen Wert.

Obwohl die klinische Besserung unseres CRIM- und Antikörper-positiven Kindes nicht nur der IMT zugeschrieben werden kann, zeigte sich das Protokoll jedenfalls als wirksam und sicher.

Schlüsselwörter

Glykogen Speicher Krankheit Typ II Kindesalter Rituximab Kardiomyopathie 

Notes

Ethical approval

The immune modulation therapy protocol was approved by the University Hospital of Split Institutional Review Board, and written informed consent was obtained from the parents. All procedures were in accordance with the ethical standards and with the Helsinki Declaration of 1975.

Conflict of interest

The authors declare that there is no conflict of interest.

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Josko Markic
    • 1
    Email author
  • Branka Polic
    • 1
  • Luka Stricevic
    • 2
  • Vitomir Metlicic
    • 2
  • Radenka Kuzmanic-Samija
    • 3
  • Tanja Kovacevic
    • 1
  • Ivana Erceg Ivkosic
    • 4
  • Julije Mestrovic
    • 1
  1. 1.Pediatric Intensive Care Unit, Department of PediatricsUniversity Hospital Centre SplitSplitCroatia
  2. 2.Division of Cardiology, Department of PediatricsUniversity Hospital Centre SplitSplitCroatia
  3. 3.Division of Neurology, Department of PediatricsUniversity Hospital Centre SplitSplitCroatia
  4. 4.Department of Obstetrics and GynecologyClinical Hospital “Sv. Duh”ZagrebCroatia

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