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Page 2 of 9 Hong et al. J Transl Genet Genom 2018;2:8. I https://doi.org/10.20517/jtgg.2018.06

Since some patients with severe forms die of overwhelming infection at a young age, proper, timely
diagnoses become very critical. Although the diagnosis of LAD-I is based on typical clinical presentation,
combined with laboratory demonstration of leukocytosis and reduction of CD18 expression, the precise
molecular characterization is required for diagnosis confirmation. Recently the use of high-throughput
[3]
targeted exome sequencing (TES) has resulted in faster sample turnaround time and more cost-effective
analysis of the causative mutations.

In this paper, we reported a rare case of a 43-day-old boy referred to our facility for severe leukocytosis,
who responded poorly to antibiotic therapy, to highlight the importance of molecular testing to definitively
establish the diagnosis when LAD-I is suspected. Moreover, the early diagnosis of immunodeficiency is
essential for optimal management such as hematopoietic stem cell transplantation (HSCT) and rehabilitation
outcomes.

CASE REPORT
The young patient’s family is of Chinese Han ethnicity; a male baby, the second neonate of unrelated parents
delivered via cesarean section after an uneventful full-term pregnancy. The proband’s birth weight was 3000 g.
A review of the family history revealed that his older sister had passed away at the age of 3 months of sepsis
with no response to various second-line and third-line antimicrobials. The patient’s condition was initially
observed when he suffered a fever at the age of 25 days after birth; diagnosed then by his neonatologist as
systemic inflammatory response syndrome (SIRS) in a local hospital. Laboratory tests revealed leukocytosis
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with neutrophil predominance [83,550 (10 /L), 70.7%] and high C reactive protein (CRP) (69 mg/L).
Intravenous (IV) antibiotics therapy (vancomycin combined with meropenem) was started and maintained
for 18 days, with a good clinical response.

Five days later, he was referred to our neonatal department because of hyperthermia and marked
neutrophilia. Physical examination upon admission reported a well-developed infant, with head
circumference of 34 cm and weighing 4140 g. Hepatosplenomegaly was noted, with liver span of 5 cm
and spleen 3 cm below costal margin. The levels of serum inflammatory markers [Table 1] were abnormal,
but cultures for bacteria and fungi were negative. Further laboratory investigations showed elevated
aminotransferase and high cytomegalovirus (CMV) PCR titers in his urine (positive) and plasma
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(3.9*10 copies/mL) samples.

After receiving the treatment of intravenous immunoglobulin (IVIG), second-line and third-line
antimicrobials in the form of cefepime, teicoplanin teiculine and cephalosporins and IV ganciclovir
(10 mg/kg/d for 14 days and 5 mg/kg/d for 7 days), he was discharged after three weeks with no fever,
declined white cell count and CMV titers and normal liver function. He continued to receive oral ganciclovir
(5 mg/kg/d) treatment after discharge.

From then on the patient experienced recurrent upper respiratory tract infections and was admitted to our
hospital with two episodes of deep infections coupled with hyperthermia and marked neutrophilia [Table 1].
At 2 months of age, a 2.5 cm × 3 cm erythematous skin area surrounding the umbilicus without pus or foul
odors and tenderness to palpation around the umbilicus was noted. The ultrasound of the umbilical cord
showed an infected urachus. The patient was treated with surgery debridement and resection of his urachus.
At the same time, he received IV cefatriaxone, teicoplanin and ganciclovir (5 mg/kg/d). Five days later, his
umbilicus had nearly returned to normal. He completed 20 days of antibiotic therapy before and after his
surgery. At 4 months of age, he developed bronchopneumonia and showed neutrophilia with elevated CRP
[Table 1]. Empiric antibiotic therapy was started after his admission and adjusted in form of cefmetazole,
cefepime, tienam, meropenem, linezolid, fluconazole and teicoplanin based on those infection indexes. He
was treated with IVIG again and IV ganciclovir (5 mg/kg/d) for 2 weeks. He recovered from his cough soon