Osteopetrosis mimicking juvenile myelomonocytic leukemia.

A 5-month-old boy developed splenomegaly, anemia, thrombocytopenia with elevated white cells, monocytosis and immature granulocytes in the peripheral blood. Bone marrow showed dysplasia without blastosis. Increased colony-forming unit-granulocyte-macrophage was found in the peripheral blood, mimicking granulocyte-macrophage colony-stimulating factor hypersensitivity. These findings fulfilled the diagnosis criteria for juvenile myelomonocytic leukemia (JMML), but no mutations in the CBL, NRAS, KRAS, or PTPN11 genes were detected. In addition to these findings severe hypogammaglobulinemia and elevated alkaline phosphatase were present. Bone X-ray showed dense and radiopaque bones with a bone-in-bone appearance characteristic of infantile malignant osteopetrosis (IMO). Genetic mutation in T-cell, immune regulator 1 (TCIRG1) was identified, confirming the diagnosis of IMO. Careful differential diagnosis including osteopetrosis, is therefore recommended in patients with clinical features and hematologic findings consistent with JMML

Un cas de cirrhose néonatale sans surcharge en fer : hépatite alloimmune congénitale

Background. Fetal liver disease is a rare antenatal disorder for which etiology is frequently unknown. Recently, congenital alloimmune hepatitis emerged as a major cause of antenatal liver disease. Its typical presentation can be as a severe neonatal liver failure with hepatic and extrahepatic iron overload, a clinical state called neonatal hemochromatosis. Methods. A pregnant woman was investigated for heterogeneous fetal hepatomegaly. Pregnancy was also complicated by fetal alloimmune thrombocytopenia. The newborn presented at birth with liver cirrhosis and mild liver dysfunction. Follow-up until 36 months showed progressive normalization of all liver parameters. All metabolic and infectious analyses were negative. Liver biopsy showed severe hepatitis with post-necrotic fibrosis and regenerative nodules. There was no iron overload. To search for immune injury, paraffine sections of the liver biopsy were stained with an antibody against the membrane attack complex (MAC, anti human c5b-9, Peter Whitington’s Lab, Children’s Memorial Hospital, Chicago, IL), the terminal complement cascade neoantigen occurring specifically in complement activation by the IgG-mediated classical pathway, and which is responsible for cell death. Results. Strong immunostaining against MAC-antigen was found in the liver of the patient, with 90% of target hepatocytes whereas in a control group of patients with other neonatal liver diseases, it was 10.8±12.5%. Because IgG in neonates originate only from the mother, it signs the alloimmune nature of the disease. Conclusion. For a long time, pathophysiology of neonatal hemochromatosis remained unsolved. Recently, it was elucidated as congenital alloimmune hepatitis. With this case, we expend the recognized clinical spectrum by showing that congenital alloimmune hepatitis can present as milder cases, without iron overload. It should be considered as a cause of unexplained neonatal liver disease, even in the absence of siderosis. Such diagnosis is of great importance regarding the necessity of immunotherapy in further pregnancies in order to avoid recurrence of alloimmune injur

Neonatal liver cirrhosis without iron overload caused by gestational alloimmune liver disease.

Gestational alloimmune liver disease has emerged as the major cause of antenatal liver injury and failure. It usually manifests as neonatal liver failure with hepatic and extrahepatic iron overload, a clinical presentation called neonatal hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected during pregnancy and who presented at birth with liver cirrhosis and mild liver dysfunction. Liver biopsy showed the absence of iron overload but strong immunostaining of hepatocytes for the C5b-9 complex, the terminal complement cascade neoantigen occurring specifically during complement activation by the immunoglobulin G-mediated classic pathway, which established the alloimmune nature of the hepatocyte injury. The infant survived with no specific therapy, and follow-up until 36 months showed progressive normalization of all liver parameters. This case report expands the recognized clinical spectrum of congenital alloimmune liver disease to include neonatal liver disease and cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost importance regarding the necessity for immunotherapy in further pregnancies to avoid recurrence of alloimmune injury

Temple-Baraitser syndrome: a rare and possibly unrecognized condition.

Temple-Baraitser syndrome, previously described in two unrelated patients, is the association of severe mental retardation and abnormal thumbs and great toes. We report two additional unrelated patients with Temple-Baraitser syndrome, review clinical and radiological features of previously reported cases and discuss mode of inheritance. Patients share a consistent pattern of anomalies: hypo or aplasia of the thumb and great toe nails and broadening and/or elongation of the thumbs and halluces, which have a tubular aspect. All patients were born to unrelated parents and occurred as a single occurrence in multiple sibships, suggesting sporadic inheritance from a de novo mutation mechanism. Comparative genomic hybridization in Patients 1, 2 and 3 did not reveal any copy number variations. We confirm that Temple-Baraitser syndrome represents a distinct syndrome, probably unrecognized, possibly caused by a de novo mutation in a not yet identified gene