Paediatrics Flashcards
What paediatric disorders are associated with an increase in HbF?
Increased HbF is seen in conditions with stressed haematopoiesis
- JMML (seen in 50%, associated with a poor prognosis)
- Diamond Blackfan anaemia
- Fanconi anaemia
- Dyskeratosis congenita
- Shwachman Diamond syndrome
What are the main differences between refractory cytopenia of childhood and adult MDS?
o Most somatic mutations in children= RAS pathway, transcription factors and epigenetic modifiers.
o Isolated anaemia uncommon. Neutropenia and thrombocytopenia more common.
o Hypocellularity commonly observed in childhood MDS (marked hypocellularity in~80%, can make distinction from AA difficult)
Those with elevated blasts should be classified as per the adult classification.
What are the morphological features of refractory cytopenia of childhood
Peripheral blood
- Ansiopoikilocytosis of RBC and plts
- Macrocytosis
- Neutrophil dysplasia
Bone marrow:
- Marked reduction in cellularity common (seen in up to 80%)
- Large clusters of proerythroblasts (>20) with maturation arrest
- Megaloblastic maturation
- Micromegakaryocytes. Dysplastic megakaryocytes.
- Neutrophil dysplasia
Discuss the features of CDA type 1
· Present with haemolytic anaemia and splenomegaly.
· 70% have macrocytosis. Red cell anisocytosis.
· Megaloblastic red cell precursors, internuclear chromatin bridging and binuclearity affecting 3-7% of erythroid precursors
· Spongy (‘swiss cheese’) appearance of heterochromatin in the majority of erythroblasts on electron microscopy.
· Autosomal recessive inheritance.
Discuss the features of CDA type 2
· Most common subtype of CDA: initially described as HEMPAS.
· Variable anaemia. ~10% require regular transfusion and some cases present with anaemia at birth.
· Variable degrees of jaundice, hepatomegaly, splenomegaly and cirrhosis. Mental retardation has been reported in some cases,
· Marked red cell anisocytosis on the peripheral blood.
· Normoblastic erythroid hyperplasia with usually more than 10% binucleate erythroblasts.
· The defining ultrastructural abnormality is a characteristic arrangement of the endoplasmic reticulum giving the appearance of a ‘double membrane’.
· Red cells from patients with CDA type II are haemolysed by some acidified sera, but not by the patients own serum.
· Autosomal recessive inheritance.
Discuss the features of CDA type 3
· Very rare.
· It is characterised by giant multinucleated erythroblasts in the marrow.
· Increased prevalence of lymphoproliferative disorders
· Autosomal dominant transmission.
What is Scwachman- Diamond syndrome?
o AR condition characterised by exocrine pancreatic insufficiency (100%), BMF (100%) and other somatic abnormalities (particularly skeletal)
o The SDS gene has an important role in the maturation of the 60S ribosomal unit, suggesting that SDS is a disorder of ribosome biogenesis.
o The spectrum of haematological abnormalities includes neutropenia (~60%), other cytopenias (20% have pancytopenia), MDS and AML (~25%).
· Varied age of leukaemic onset: 1 to 43 years.
· Unexplained preponderance of leukaemia in males
· Often has features of MDS, poor prognosis.
· SDS patients treated with cytotoxic drugs usually fail to regenerate normal haematopoiesis.
What are the haematological features of Pearsons Syndrome
· Anaemia +/- pancytopenia
· Ring sideroblasts (i.e. sideroblastic anaemia).
· Vacuolation of the myeloid and erythroid precursors.
What is Diamond-Blackfan anaemia?
· Autosomal dominant, congenital form of pure red cell aplasia with variable somatic abnormalities.
- 93% present within the first year of life.
· Normochromic, macrocytic anaemia with reticulocytopenia.
· Normal or often increased platelet counts
· Normal or slightly decreased leukocyte counts
· Normocellular BM with selective deficiency in erythroid precursors (erythroblasts <5%)
· Elevated erythrocyte deaminase activity and elevated fetal haemoglobin
· MDS, AML and AA have been reported
· A number of different genetic defects have been described that involve ribosome biosynthesis
Discuss the features of congenital neutropenia
· Heterogenous group of disorders
· Neutropenia usually recognised at birth, is <0.2 and usually associated with severe infections.
· Haemoglobin and platelet counts usually normal.
· BM shows maturational arrest at the level of the promyelocyte/ myelocyte stage- promyelocytes usually abundant.
· Mutations in ELANE (gene encoding neutrophil elastase) are the most frequent cause of congenital neutropenia.
· Can develop into AML (25% by 25yrs) or MDS.
· MDS/ AML usually associated with acquisition of mutations involving the GCSF receptor.
What is cyclical neutropenia?
· Usually autosomal dominant.
· Characterised by a neutrophil count that usually reaches a nadir with a 21 day period.
· Around the nadir, the patient may develop mouth ulcers or fevers.
Studies have identified mutations in the neutrophil elastase gene and leads to transient arrest at the promyelocyte stage.
What is Thrombocytopenia with Absent Radii (TAR)?
· AR disorder characterised by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia.
· Often have haemorrhagic manifestations at birth. Plt count is usually <50.
· The leukocyte count can be normal or raised, sometimes up to 100 (‘leukaemoid reaction’)
· Bone marrow cellularity is normal. Megakaryocytes are reduced or absent.
· Very good prognosis after infancy with no reports of AA or leukaemia.
What is Congenital Amegakaryocytic Thrombocytopenia?
· Rare disorder, presents in infancy, characterised by isolated thrombocytopenia and reduction/ absence of megakaryocytes.
· Genetically heterogeneous with AR and X-linked subtypes.
· Approximately 50% develop AA, usually by age 5.
· Treatment of choice is HSCT
· Mutations in the MPL gene have been identified in some patients.
What is transient erythroblastopenia of childhood?
· Form of pure red cell aplasia that is self-limited and occurs in children 1-4yrs of age
· FBC demonstrates a normocytic anaemia and reticulocytopenia. Thrombocytosis occurs not uncommonly.
· Characterised by the absence or a significantly reduced quantity of erythroblasts in the bone marrow without underlying congenital red blood cell abnormalities.
· Bone marrow biopsy is otherwise normal.
What is infantile pyknosis?
- Poorly understood condition.
- Probably due to transient glutathione peroxidase deficiency which results in altered vitamin E and fatty acid metabolism.
- Usually presents at 1-6 weeks of age.
- More common in preterm neonates.
- Blood film is usually characteristic with changes of oxidative haemolysis.
- The anaemia is moderate to severe and often requires transfusion.
- Usually resolves spontaneously by 3 months of age.
