Cause and Natural Course of Pediatric-Onset Mastocytosis
Cause and Natural Course of Pediatric-Onset Mastocytosis
This study will evaluate children with mastocytosis, a disease of excessive mast cells in
 tissues such as skin and bone marrow, to identify the cause of the disease and describe its
 course. Mast cells can release chemicals that cause itching, blisters, flushing, bone pain,
 and abdominal pain. Usually, mastocytosis in children involves the skin only and is of
 limited duration. This study, however, will focus on children with more severe disease that
 more closely resembles adult-onset mastocytosis.

 Patients up to 21 years of age with childhood-onset mastocytosis may be eligible for this
 study. Candidates must have one or more of the following abnormalities, which indicate severe
 disease: enlarged liver or spleen; diffuse skin involvement; history of gastrointestinal
 bleeding or peptic ulcer; bone marrow biopsy with abnormal mast cells either in number or
 shape; elevated blood levels of the enzyme tryptase; or abnormal hemoglobin, white blood
 cells, platelets, or clotting factors.

 Participants will have a medical history and physical examination; various blood tests,
 including studies to identify genetic changes that are important in the growth, development,
 and functioning of human mast cells; and bone marrow aspiration and biopsy. For the bone
 marrow procedure, the skin over the hipbone and the outer surface of the bone itself are
 numbed with an injection of local anesthesia. Then, a special needle is inserted into the
 hipbone and about 2 tablespoons of bone marrow are drawn into a syringe. Another needle is
 then inserted through the first needle to collect a small piece of the bone marrow. Pain will
 be managed according to the individual patient s needs. Additional procedures, such as a
 gastroenterology consultation, colonoscopy to examine the colon, or computerized axial
 tomography (CT) or ultrasound of the abdomen to assess the liver and spleen, may be done if
 medically indicated. Standard medical treatment, including antihistamines for itching or
 steroids for abdominal cramping or diarrhea, will be recommended as appropriate.

 Patients biologic parents may also be enrolled to provide a blood sample for genetic analysis
 and a bone marrow aspirate and biopsy for clinical and research purposes.

 Patients will return to NIH once a year for follow-up evaluations until their disease is
 stable or until the 5-year study ends.

 ...
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