Cause and Natural Course of Pediatric-Onset Mastocytosis

Mastocytosis in infants and children is an unusual disease characterized by an excess of mast cells in tissues. In pediatric onset mastocytosis, disease is usually localized to the skin and disease is considered to be of limited duration. However, a subset of children appear to develop a clinical picture resembling that observed in adults who have adult-onset disease. This study will focus on children with more severe mastocytosis in an attempt to define its pathogenesis, focusing on mutations and polymorphisms in genes regulating mast cell proliferation and survival to determine if they might contribute to this disease pattern. If severe pediatric-onset disease does not fit within the existing classification, new criteria of diagnosis must be proposed for the pediatric age group.

This study will examine children and young adults age birth to 21 years with pediatric-onset disease previously enrolled on NIAID mastocytosis protocols, or as a result of physician referral, which have disease more consistent with adult-onset disease or parameters associated with increased morbidity. The evaluation may include serum tryptase, blood count, bone marrow biopsy and aspirate, morphology and mutational analysis. Subjects may be asked to return in 12-24 months for assessment. If relevant mutation effecting mast cell growth and function are identified, such mutations will be sought in the biologic parents as appropriate, but only when such mutations are believed to be germ line (not somatic) mutations. This study will aid in the understanding of the characteristics of severe mastocytosis in the pediatric age group.

• INCLUSION CRITERIA:

Children with tissue-diagnosed pediatric-onset mastocytosis formerly enrolled in protocols 90-I-0120, and 93-I-0136 or per physician referral with more severe disease as indicated by one of the following parameters:

• Hepatomegaly or splenomegaly;
• Diffuse cutaneous mastocytosis;
• History of gastrointestinal bleeding or peptic ulcer disease;
• Bone marrow biopsy with abnormal numbers or shaped mast cells or abnormal flow cytometry;
• Serum tryptase greater than 20ng/ml;
• Hematologic abnormalities such as an increase WBC, thrombocytosis, and/or an increase in PT and/or PTT.

Inclusion criteria

-SUBJECT:

• Age birth to 21.0 years of age at the time of entry into the protocol
• Diagnosis of mastocytosis by skin examination or histologic evidence in a skin or bone marrow biopsy
• Subject has a primary medical care provider outside the NIH
• Subject or parent or guardian is able to give informed consent

Inclusion criteria

-RELATIVE:

• A biological relative with or without the diagnosis of mastocytosis by skin examination or histologic evidence in a skin or bone marrow biopsy
• Subject has a primary medical care provider outside the NIH

Exclusion criteria

SUBJECT:

• Age greater than or equal to 21.0 years
• No primary care physician
• Has AIDS or is HIV Positive