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