Paediatrics: Failure of red cell production (pure red cell aplasia)

Failure of red cell production (pure red cell aplasia)

Causes

·  Transient erythroblastopenia of childhood (TEC).

·  Diamond–Blackfan syndrome.

·  Drugs.

·  Viral, e.g. parvovirus B19.

·  Isoimmune haemolytic disease in newborn, e.g. anti-Kell.

·  Congenital dyserthropoietic anaemia (CDSs).

·  Megaloblastic anaemia (aplastic phase).

Diamond–Blackfan syndrome (congenital red cell aplasia)

This is a hereditary condition of variable genetic inheritance that, by an unknown defect, leads to a specific reduction in bone marrow RBC pro-duction. The genetic basis remains unclear, however, mutations in the gene which codes for RPS19, a small ribosomal protein on chromosome 19q13.2, are found in approximately 25% of patients. The familial form (au-tosomal recessive) accounts for 10–20% of cases. The rest are sporadic.

Presentation

Presents in the first year of life in 95% (25% with severe anaemia in the first 6mths). Occasional late presentations with variable phenotypes can occur and 15–25% of cases undergo remission. The syndrome is associ-ated with:

·  Dysmorphic features; cleft palate, hypertelorism (Cathie’s facies).

·  Thumb abnormalities in 10–20%; triphalangeal thumbs; absent radii.

·  Deafness.

·  Renal defects (>50%).

·  CHD.

·  Musculoskeletal defects.

·  Short stature and growth retardation.

Investigations

FBC shows normochromic anaemia with reticulocytes ‘fall’ (<0.2%). WCC and platelet count are usually normal. Bone marrow aspirate and trephine shows absent red cell precursors, but is otherwise normal.

Treatment

Trial of oral prednisolone 2mg/kg/day (preferably once they are immune to varicella zoster). Wean over several weeks. Some 70% of patients have an initial response, but most will need, but often cannot tolerate, a main-tenance dose. Give regular monthly RBC transfusion with iron chelation if unresponsive to steroids. BMT can be curative.

Prognosis

Although 20% spontaneously resolve, there is significant mortality and morbidity in the rest from steroid treatment and blood transfusion relat-ed complications (e.g. iron overload).

Transient erythroblastopenia of childhood

An acquired, self-limiting red cell aplasia. This condition is idiopathic or secondary to bacterial or viral infection (e.g. parvovirus B19, EBV), drugs, malnutrition, or congenital haemolytic anaemia (e.g. hereditary spherocy-tosis). Incidence is equal in boys and girls.

Typically presents at <5yrs of age with insidious onset of anaemic symp-toms in the previously well child. Examination is usually normal except for signs of anaemia. The patient may have a preceding viral or bacterial infection. FBC shows normocytic, normochromic anaemia, absent reticu-locytes, and normal WCC and platelet count. Bone marrow is normal except for markedly reduced erythroid precursors.

Treatment

·Remove any underlying cause, e.g. drugs.

·Monitor FBC to ensure this is not a leukaemic prodrome.

·Blood transfusion if required.

The condition spontaneously resolves (signaled by a rise in reticulocyte count), usually within weeks, but occasionally may take up to 6mths.