Infantile pyknocytosis
Authors: Clare Rees, Kirstin Lund, Barbara J. Bain
Journal: American Journal of Hematology (2018)

A newborn baby boy, born at term to consanguineous parents of Moroccan origin, presented aged 2 weeks with jaundice. He was breastfeeding well, gaining weight and not lethargic. His blood count showed: white blood cells 22.3 × 109/L, hemoglobin concentration (Hb) 63 g/L, mean cell volume 102 fL, and platelet count 596 × 109/L. Total bilirubin was 396 μmol/L and reticulocytes were 404 × 109/L (20.5%). He had been jaundiced at 48 h of age and was treated with double phototherapy for 24 h; a point-of-care capillary Hb had been 181 g/L at that time. There was RhD incompatibility; his mother was a primigravida and had received appropriate anti-D prophylaxis and had negative antibody screens throughout. The direct antiglobulin test was negative. His peripheral blood film (Images) showed keratocytes, irregularly contracted cells, blister cells, polychromasia, and some Howell-Jolly bodies, consistent with oxidative haemolysis. A Heinz body screen was positive. There was no history of exposure to any oxidizing agents in either the mother or baby. Pre-transfusion investigations included glucose-6-phosphate dehydrogenase (G6PD) assay, which was 18.8 u/gHb (pediatric normal range 10-15). (G6PD level in the mother was normal at 10.1 u/gHb.) Pyruvate kinase was high at 18.9 u/gHb (adult normal range 6.2-14.2). High performance liquid chromatography was normal for age: hemoglobin A 54%, hemoglobin A2 1.1%, and hemoglobin F 46.2%. Hemoglobin mass spectrometry was normal. Glutathione peroxidase level was 9.2 u/gHb (adult normal range 13.0-30.0). Selenium was 0.77 μmol/L (adult normal range 0.25-0.6). In view of the morphological findings and the reduced glutathione peroxidase, a diagnosis of infantile pyknocytosis was made. Subsequent analysis of the GPX1 gene disclosed no mutation. The baby was transfused red cells and discharged home. Follow-up blood tests showed resolving hemolysis; at 2 months of age Hb was 104 g/L and reticulocytes 81 × 109/L with no further need for transfusion. Infantile pyknocytosis is a poorly understood condition, first described by Tuffy et al. in 1959.1, 2 These authors commented on 'markedly distorted and contracted red cells', which they also called "burr cells". Acanthocytes and Howell-Jolly bodies can also be present, reflecting splenic overload. The "pyknocytes" are keratocytes and other dense deformed cells. They appear as hyperdense cells on automated instrument scatter plots. The diagnosis rests on the characteristic blood film features of oxidant damage, with other conditions such as G6PD deficiency and exposure to an exogenous oxidant being excluded. As in our patient, there can be a transient neonatal deficiency of glutathione peroxidase, in the absence of any mutation in the gene. Other cases are attributed to deficiency of selenium, a component of glutathione peroxidase. Extracorpuscular factors may also be relevant as pyknocytes can reappear rapidly after exchange transfusion.3 Premature infants can also develop haemolytic anemia with pyknocytes as a result of vitamin E deficiency.4 Management is supportive since spontaneous resolution occurs. Nothing to report.