Intestinal hypoganglionosis is a rare innervation disorder that provides numerous nutritional, medical and surgical challenges. In this case report, we present a case of a newborn with intestinal hypoganglionosis leading to intestinal failure and intestinal failure-associated liver disease who responded to Omegaven™, a fat emulsion comprised of omega-3 fatty acids. Omegaven™ has been shown to be beneficial in the management of cholestatic liver injury. Clinical success with Omegaven™ was seen in this patient with a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and complete resolution of cholestasis with a direct bilirubin of zero within two weeks of initiation of Omegaven™. No current guidelines for the diagnosis and management of hypoganglionosis are available. We recommend a multidisciplinary approach and the use of novel therapies such as fat emulsions composed of omega-3 fatty acids for improved patient outcomes. Appropriate compassionate use protocols should be obtained from the Food and Drug Administration prior to initiation of Omegaven™.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Cholestasis ; Compassionate Use Trials* ; Diagnosis ; Empathy* ; Emulsions ; Fatty Acids, Omega-3 ; Hirschsprung Disease ; Humans ; Infant, Newborn ; Liver ; Liver Diseases ; Parenteral Nutrition, Total ; United States Food and Drug Administration

BACKGROUND: Chronic Myelogenous Leukemia (CML) is the first proven disease in which gene abnormality, t(9;22)(q34;q11) can cause the disease to occur in humans. Recently, targeted therapy with STI571 (GleevecTM), signal transduction inhibitor for BCR-ABL kinase was developed and can induce cytogenetic remission in patients with CML. Hypermetaphase-FISH (HMF)/Interphase-FISH (I-FISH, Fluorescence in situ hybridization) aiming specific chromosomal abnormalities are unambiguous quantitative molecular genetic methods for individual Philadelphia (Ph1) chromosome positive cells. We evaluated the change of Ph1 chromosome in CML patients during STI571 therapy using HMF/I- FISH. METHODS: Twenty one patients with CML were treated with STI571 which was provided from Norvatis pharmaceutical company as Expanded Access Program for Compassionate Use from May 2001 at the doses of 200-600 mg/day orally. Median age of this cohort was 37 years old and median follow up duration was 113 days (48~165 days). HMF or I-FISH using bone marrow or peripheral blood were performed on the sample at baseline, day 14, day 28 and then monthly. RESULTS: Complete cytogenetic responses which were assessed by HMF/I-FISH counting several hundreds cells were found in 8 of 21 patients. Among them, 4 of 10 chronic phase, 2 of 2 accelerate phase and 2 of 8 blastic crisis patients achieved cytogenetic complete response. One patient with blastic crisis was relapsed after achieving cytogenetic complete response. Grade III-IV thrombocytopenia and neutropenia were noticed in 8 and in 7 patients respectively, but there were no major bleeding episodes nor neutropenic fever. CONCLUSION: BCR-ABL tyrosine kinase inhibitor, STI571 was tolerable for patients with CML. The majority of patients achieved hematologic remission and 8 out of 21 patients achieved complete cytogenetic response regardless of their disease stage. Cytogenetic response of Ph1 chromosome can be quantified accurately with HMF/I-FISH.
Adult ; Bone Marrow ; Chromosome Aberrations ; Cohort Studies ; Compassionate Use Trials ; Cytogenetics ; Fever ; Fluorescence ; Follow-Up Studies ; Fusion Proteins, bcr-abl ; Hemorrhage ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Molecular Biology ; Neutropenia ; Philadelphia Chromosome* ; Phosphotransferases ; Signal Transduction ; Thrombocytopenia ; Imatinib Mesylate