FM OCTOBER 2018 ISSUE - digital edition

However, at age 4, the
child was brought to Lilawati
Hospital and Research DURING DISCUSSIONS
Center, Mumbai, to consult WITH OTHER DOCTORS, SHE
with Dr. Swati Kanakia, a REALIZED THAT PERHAPS
pediatric hemato-oncologist.
HER CHOICE OF KEYWORDS
The patient presented with
WAS NOT CORRECT.
bleeding in the skin, another
intracranial hemorrhage,
and low platelet count. An
MRI showed calcification in
the basal ganglia and evidence of the previous intracranial
bleeding. Based on the history, the patient was started on
IVIg for treating low platelets. Further, even though normally
platelets are not given as therapy in such cases as they
would be expected to be destroyed in the body, this patient
was again given platelets as well because of the intracranial
hemorrhage, and started with cyclosporine syrup.
In addition, Dr. Kanakia observed certain morphological
abnormalities including short stature, high arched palate,
low set ears, and wider wrists than normal. Wider wrists are
typical signs of rickets and an X-ray of the wrist was done
which indeed showed typical signs of rickets. Blood tests
for vitamin D, calcium, and phosphorous however did not
corroborate with the clinical findings for rickets.
This was indeed an atypical case where the patient
had an early onset of ITP, was not responsive to treatment
over long periods of time, had two intracranial hemorrhages,
calcification of basal ganglia and showed signs of
abnormal facies. In addition to these, she was strongly
positive for alloantibodies against red blood cells as
evidenced in a direct Coomb’s test and thyroid antibodies
causing hypothyroidism. Such autoantibodies are
evidence of autoimmunity. Dr. Kanakia was not satisfied
with the diagnosis and treatment being offered to the
patient, and continued to search for a more accurate
diagnosis and better treatment options. She searched the
OMiM database for other similar cases, but was not able to
come up with anything similar. During discussions with other
doctors, she realized that perhaps her choice of keywords
was not correct. She was including the
keyword ‘rickets’ due to the wider wrists
that are characteristic of rickets. However,
once she replaced ‘rickets’ with ‘metaphyseal
dysplasia’, she was able to find a very similar
condition called spondyloenchondrodysplasia
with immune dysregulation (SPENCDI).
As per the description, ‘SPENCDI is an
immunoosseous dysplasia combining the
typical metaphyseal and vertebral bone
lesions of spondyloenchondrodysplasia
(SPENCD) with immune dysfunction and
neurologic involvement’ The patient’s
condition seemed to fit well with the
description.
SPENCDI is caused by a homozygous
mutation in the APC5gene on chromosome
19p13. Genetic testing was carried out, and
consistent with the clinical symptoms, the
patient was found to carry a homozygous
deletion in the APC gene that results in a
truncated protein. The patient’s parents also
underwent genetic testing, and they were
found to carry the heterozygous mutations.
Based on this genetic identification, the
patient had a confirmed diagnosis of
SPENCDI and was accordingly continued on
cyclosporine. The dosage of cyclosporine
was kept at a minimum dose just to maintain
the platelet levels at a safe count of 30,000-
40,000/uL. The patient is doing well as of
now.
The genetic identification was not only
important for adequate treatment and
management of the patient, but would also
be important in case the parents decided to
have another child. Prenatal testing can be
used to determine whether the child would
be homozygous or heterozygous, allowing
for the option to terminate the pregnancy if
required. Such prenatal testing may therefore
prevent another child with the same genetic
disorder. Genetic testing can also be done for
close family members to assess hereditary
mutations.
“Accurate diagnosis gives the patient/
patient’s family a sense of closure and helps
them prepare for their next child. Even in
this age of technological advances, clinical
judgement is extremely important. To be
able to diagnose accurately, it is important to
understand which tests to run,” Dr. Kanakia
shares her learnings from this case.
DR SHIVANEE SHAH
OCTOBER 2018 / FUTURE MEDICINE / 57