FM DECEMBER 2018 ISSUE - digital edition

case reports
FALLING NEUTROPHILS
A case of severe congenital neutropenia leading to recurrent infections
Severe congenital neutropenia is a chronic blood
disorder due to an accumulation of granulocyte
precursors in the bone marrow, resulting in recurrent
fever and recurrent infections, including respiratory, skin and
oropharyngeal infections, most often due to staphylococci
and streptococci. Neutropenia is apparent soon after birth
and can lead to osteoporosis or even leukaemia, affecting
about 1 in a million worldwide. While the cause of severe
congenital neutropenia is unknown for about one-third
of the people with the disorder, mutations in different
genes are known to be responsible for the rest; about
50% of the cases are due to mutations in the neutrophils
elastase (ELANE)gene while 10% are due to mutations in
the HS-1-associated protein X-1 (HAX1) gene. Mutations in
other genes such as the Wiskott-Aldrich syndrome (WAS)
gene, that encodes for the WAS protein (WASP), may also
result in severe congenital neutropenia. Mutations in the
ELANEgene cause misfolding in the 3D structure of the
protein. This results in the accumulation of the neutrophil
elastase protein within the neutrophils, eventually leading
to the death of the neutrophils. HAX1 is a protein required
for regulating apoptosis. Mutations in the
HAX1 gene results in premature death
of the neutrophils. These mutations are
often isolated, sporadic cases. However,
mutations in the ELANEgene are inherited
in an autosomal dominant manner, while
mutations in the HAX1gene are autosomal
recessive.
Here is a case of three-year-old Shama
(name changed), who presented to the
ICU at Lilawati Hospital at Mumbai with
fever, vomiting and rashes on the thighs
and around the mouth. Dr. K. N. Shah, the
consulting paediatrician, observed that
the child had tachycardia and tachypnea
with a palpable liver that was soft and
non-tender, but no palpable spleen and
lymph nodes. Laboratory tests revealed
that her white blood counts, CRP, PCT and
ESR were high. However, her neutrophil
count was low, and the monocyte count
50 / FUTURE MEDICINE / DECEMBER 2018