Background: A somatic activating GNAS mutation leads to the triad of café au lait macules, fibrous dysplasia and precocious puberty known as Mc Cune Albright Syndrome (MAS). We present a patient with bone marrow failure as a rare non-endocrine complication of MAS.
Clinical case: A 2-year-old girl with neonatal giant cell hepatitis, a large right sided café au lait spot and fibrous dysplasia was diagnosed with MAS. The severe polyostotoc fibrous dysplasia lead to a total of 12 fractures, 18 operations, short stature and wheel chair dependency. Over the following years, the patient developed gonadotropin-independent precocious puberty, hyperthyroidism, FGF-23 mediated phosphate wasting and a breast duct papilloma which were treated accordingly. At the age of 14 years the patient felt fatigued and the blood count showed pancytopenia. No signs of infection, haemolysis or malignancy were found in the hematologic work up. Her spleen was enlarged to 166 mm. A bone marrow biopsy of the iliac crest revealed fibrous dysplasia without bone marrow cells. In bone and breast tissue a mutation of the GNAS Locus: (c.601C>T,p.R201C) with activation of the MAPK pathway (pERK positive) was detected. Monthly transfusions had to be initiated 6 months after the onset of pancytopenia. The splenomegaly progressed, causing increasing abdominal pain and respiratory distress. Therefore, a splenectomy had to be performed 1 year after the onset of pancytopenia. Histology confirmed extramedullary haematopoiesis in the spleen. After splenectomy pancytopenia resolved. The patient has now been without blood transfusion for 1 year.
Conclusion: Though fibrous dysplasia is a hallmark of patients with MAS, bone marrow failure is rarely observed. It is still unknown, whether the grade of fibrous dysplasia, the extent of bone reconstruction surgery, the presence of endocrinopathies or a different pathogenetic mechanism trigger the onset of bone marrow failure. Treatment of the extramedullary haematopoiesis with splenectomy is therapeutic and leads to remission of pancytopenia.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology