Objectives To detect
gene mutation associated with
hemophagocytic lymphohistiocytosis (HLH) and to identify
mutation spectrum and clinical feature in HLH in
children.
Methods Thirty-seven (37) pediatric
patients diagnosed with HLH according to 2004 clinical and
laboratory criteria were enrolled from July 2012 to November 2015.
Nucleotide sequences of all
exons and their flanking intronic sequences of ten
genes associated with HLH were amplified with
PCR followed by direct sequencing.
Point mutation analysis was performed after the direct sequencing. Results The median age of all the 37
patients was 2.6 years. The median ages of
patients with
gene mutation (n=22) and without
gene mutation (n=15) was 2.09 years and 2.67 years, without statistical significance. Twenty-two
patients were identified with
gene mutations. All of them were heterozygous. UNC13D
mutation (50%) is of the highest frequency in the above
genes. The splicing
mutations (38%) were the main type of UNC13D
mutations,and
missense mutations or frame-shift
mutations were also found. There was no statistical difference in ages of onset and
laboratory data of
neutrophils,
thrombocytes,
NK cell activities within the three groups multi-site
mutations, single-site
mutations and no
mutations.
EBV infection was detected in 70.3%
patients. In
mutation group, one
patient died when he was in the period of inducing remission, and four
patients were relapsed. Among them four
patients were infected with
EBV and one
patients was negative at the onset while positive in
recurrence. Conclusions UNC13D was the predominant causative
gene in the
Chinese population according our data. There was no significant relevance between
age of onset, severity of
disease and
gene mutations.
Attention should be paid to a
patient with HLH
gene mutation infected by
EBV, which it might mean a poor
prognosis.