Osteopetrosis due to Homozygous Chloride Channel ClCN7 Mutation Mimicking Metabolic Disease with Haematological and Neurological Impairment

Abstract

We report on the fatal clinical course of a 3 year old male Turkish patient suffering from osteopetrosis caused by a homozygous mutation in the chlorid channel gene ClCN7 with developing pancytopenia and severe neurological impairment. Hepatosplenomegaly due to extramedullary hematopoesis, severe transfusion-dependent anemia and growth failure initially suggested metabolic or oncologic disorder. Particular haematological parameters like tear drop cells basophilic punctation of the polymorphonuclear cells in the absence of haemolysis caused the diagnostic X-ray investigations of the skull and vertebral column. Raised serum creatinkinase-BB isoenzyme and genetic testing were in line with the diagnose of osteopetrosis at an age of 2œ years.

Conclusion: Osteopetrosis is a rare but considerable differential diagnose for unclarified change in haematopoetic cell lines combined with severe neurological symptoms mimicking metabolic or haematological disease.

Because of this rare disease a consensus protocol for diagnostics, treatment and follow up of patients suffering from osteopetrosis is recently worked out from the European Group of Blood and Marrow Transplantation (EBMT) and the European Society for Immundeficiencies (ESID) to build up a central registry for this disease (available by [e-mail]).

Zusammenfassung

Ein türkischstämmiger Junge erkrankte im Alter von 2œ Jahren an einer schweren Panzytopenie unter schwerer neurologischer Beeinträchtigung und verstarb im Alter von 3 Jahren. Hepatosplenomegalie, schwere transfusionsbedürftige Anämie und Wachstumsstörungen ließen anfänglich an eine onkologische Erkrankung oder einen Stoffwechseldefekt denken. Speziell hämatologische Merkmale wie basophile Tüpfelung der polymorphkernigen Zellen bei fehlenden Hämolysezeichen führten zur radiologischen Untersuchung des Skeletts; erhöhte Kreatininkinase-BB-Isoenzym-Werte sowie die genetische Untersuchung auf Osteopetrose führten schließlich zur Diagnose im Alter von 2œ Jahren. Einzelne Mutationen im Bereich des ClCN7-Gens werden für die neuronale und retinale Pathogenität verantwortlich gemacht.

Schlussfolgerung: Die Osteopetrose ist eine seltene aber wichtige Differenzialdiagnose bei unklaren hämatologischen Veränderungen und mit schweren neurologischen Symptomen.

Wegen der Seltenheit dieser Erkrankung ist ein Konsensusprotokoll bezüglich Diagnostik, Behandlung und Nachsorge im Auftrag der EBMT (European Group of Blood and Marrow Transplantation) und der ESID (European Society for Immundeficiencies) in Ausarbeitung, um ein Zentralregister bezüglich dieser Erkrankung erstellen zu können (erhältlich bei [e-mail]).

Key words

ceroid lipofuscinosis - CK-BB - ClCN7 - neurodevelopmental delay - osteopetrosis - pancytopenia

Schlüsselwörter

Zeroidlipofuszinose - CK-BB - ClCN7 - Entwicklungsverzögerung - Osteopetrose - Panzytopenie

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