METHODS
The patient was administered IV fluids and IV antibiotics after sending a blood sample for culture. He was treated symptomatically with antipyretics, antiemetics, antihistamines, and antacids. The results of initial blood investigations are presented in Table 1. As the blood culture came negative and the fever subsided antibiotics were de-escalated and the child was started on IV methylprednisolone, given elevated inflammatory markers.
Table 1
Ultrasonography abdomen revealed a smaller size of the left lobe of the liver and the spleen was not visualized. CT abdomen confirmed asplenia. During the hospital stay, the child had recurrent episodes of vomiting followed by dull activity. Hence the child’s vitals monitoring was done, which showed high blood pressure. The patient had an episode of seizure activity and upward rolling of the eyeballs hence was started on IV antiepileptics and anti-hypertensive infusion. However, MRI brain, MR venogram, and EEG did not reveal any significant findings. USG renal Doppler was normal and endocrinological workup was inconclusive for hypertension. As the patient’s blood pressure settled, the anti-hypertensive infusion was slowly tapered and stopped and oral anti-hypertensives were administered.
As the patient was having persistent fever spikes, elevated ferritin, LDH levels, liver enzymes, thrombocytosis, leukocytosis, asplenia, and dysmorphic facies, a multitude of evaluations were performed to rule out various pathologies. Hb electrophoresis was found to be normal and the patient was negative for JAK 2 mutations. Bone marrow aspiration revealed erythroid hyperplasia with normoblastic and megaloblastic maturation, confirming hemolysis. Low bilirubin levels despite continuous hemolysis raised a suspicion about a possible defect in the heme synthesis pathway. Whole exome sequencing detected a pathogenic variant responsible for the reported phenotype. A homozygous nonsense variant in Exon 2 of the HMOX1 gene (chr22: g.35383212>T; Depth: 84x) that results in a stop codon and premature truncation of the protein at codon 44 (p. Arg44Ter: ENST00000216117.9) was detected (Table 2). The observed variant lies in the “Heme oxygenase” domain of the HMOX1 protein.
Table 2