A 2-year-old Chinese boy was referred to Hospital UKM for investigation of recurrent episodes of dark-coloured urine and pallor since birth. He was born prematurely at 34 weeks gestation and developed severe early-onset neonatal jaundice requiring exchange blood transfusion. Screening at birth showed Glucose-6-phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination revealed pallor, jaundice and mild hepatomegaly. Results of laboratory investigations showed a hemoglobin level of 11.0 g/dl with a hemolytic blood picture, reticulocytosis of 20% and red cell G6PD activity reported as undetectable. The patient's DNA was analysed for G6PD mutations by PCR-based techniques and DNA sequencing and results showed a 24 bp deletion of nucleotide 953-976 in the exon 9 of the G6PD gene. DNA analysis was also performed on blood samples of the patient's mother and female sibling confirming their heterozygous status, although both showed normal red cell G6PD activity levels. The patient was discharged well and his parents were appropriately advised on the condition and the importance of taking folic acid regularly. This is a first case report in Malaysia of G6PD deficiency causing chronic-hemolytic anemia. The rare 24 bp deletion causes the G6PD Nara variant, previously reported only in two other unrelated males, a Japanese and a Portuguese both with chronic hemolytic anemia.
Familial distal renal tubular acidosis (dRTA) can be caused by mutations in the Cl2/HCO32 exchanger of the renal Type A intercalated cell, kidney AE1/SLC4A1. dRTA-associated AE1 mutations have been reported in families from North America, Europe, Thailand, Malaysia, Papua-New Guinea, Taiwan, and the Philippines, but not India. The dRTA mutation AE1 A858D has been detected only in the context of compound heterozygosity. We report here two unrelated Indian patients with combined hemolytic anemia and dRTA who share homozygous A858D mutations of the AE1/SLC4A1 gene. The mutation creates a novel restriction site that is validated for diagnostic screening.
A rare syndrome of hypertension, seizures and intracranial bleed has been reported among patients with congenital hemolytic anemia who underwent multiple blood transfusions. We report this syndrome in a 12-year-old Malay girl with hemoglobin E-beta-thalassemia, who underwent intensive transfusion and subsequently had headache, visual loss, severe hypertension and seizures. A comprehensive literature review revealed 30 patients with this syndrome, of whom 15 had intracranial bleed and 12 among these 15 died. A less-intensive transfusion regimen among patients with chronic hemolytic anemia and prompt detection and management of hypertension may prevent this potentially fatal syndrome.
Extramedullary hematopoiesis (EH) is a rare but well-known compensatory mechanism of red blood cell production when the normal site of red bone marrow is unable to produce sufficient number of red blood cells. When the body demands for erythrocyte cells is high this lead to EH. This occurs mainly outside the bone marrow, usually paraspinally and sites which are normally observed in the fetus as in the liver, spleen, lymph nodes and less frequently at other sites such as adrenal, thymus, kidneys, pleura, breast, skin, gastrointestinal tract, dura mater and brain.This is more frequent in thalassaemia major (incidence up to 15% of cases), in myelofibrosis, myeloproliferative diseases (polycythemia rubra vera, chronic myeloid leukemia,), hemolytic anemias such as hereditary spherocytosis, pyruvate-kinase deficiency, medullary tuberculosis and in Paget’s disease of the bone. In some cases the cause of the EH are not identified [3]. We describe a case of EH in the presacral space that mimicked an ovarian mass on ultrasound in a patient with beta-thalassaemia intermedia.