Asian Pacific Journal of Tropical Medicine (2012)667-668
Document heading doi:
Refractory hypocalcemia precipitated by dual infection with typhoid
fever and hepatitis A in a patient with congenital hypoparathyroidism
Suman S Karanth
*, Ram Bhat, Anurag Gupta
Kasturba Medical College, Manipal, Manipal University, Karnataka, India
Contents lists available at ScienceDirect
Asian Pacific Journal of Tropical Medicine
ARTICLE INFO ABSTRACT
Received 10 March 2012
Received in revised form 15 May 2012
Accepted 15 July 2012
Available online 20 August 2012
*Corresponding author: Dr. Suman S Karanth, #17 OPD Block, Department of
Medicine, Kasturba Medical college, Manipal, Manipal University, Karnataka, India.
Hepatitis A can present infrequently as cholestatic
hepatitis. Typhoid fever can also present with acute
hepatitis along with cholestatic jaundice. Normally this
cholestatic phenomenon is clinically benign. However
we would like to report this perplexing case where
both these infections combined to produce refractory
hypocalcemia in a patient with previously stable congenital
2. Case report
A 17 yr old boy, a known case of congenital hypoparathyroidism
on regular treatment of oral calcium supplementations,
presented to us with fever and jaundice for 8 days associated
with 2 episodes of generalised tonic-clonic seizures
on day 3 of fever. He was diagnosed to have congenital
hypoparathyroidism at 2 ½ years of age when he presented
with febrile seizures and hypocalcemia. There were no signs
of rickets, steatorrhea or alkalosis at the time. Skull and
wrist rhoentograms were normal. But computed tomography
of the brain showed extensive bilateral deep basal ganglion
calcification. Patient was receiving regular oral calcium
supplementation (1 g tid) with calcitriol (0.25 microgm bd)
ever since and serial serum calcium levels were normal.
When the patient presented to us 8 days later, he continued
to have high grade fever with chills and rigors and without
further episodes of seizures. Clinical examination revealed
the stigmata of congenital hypoparathyroidism with
dystrophic nails and teeth. There was, however, no evidence
of growth retardation or developmental delay. Chvostek
and trousseau sign were positive. He had no history of any
preexisting liver disease and denied alcohol abuse, the use
of drugs known to be hepatotoxic, blood transfusion , drug
addiction, unsafe heterosexual and/or homosexual exposure
or surgery in the previous 6 months.
Vitals were stable except for febrile state. Icterus was
present. Liver was enlarged 3 cm below the right costal
margin and a soft spleen was palpable 2 cm below the left
costal margin. Investigations revealed severe hypocalcemia
phosphorus levels (5.4 mg/dL), and hypomagnesia levels
(11.2 mg/dL) with a predominant direct hyperbilirubinemia
glutamic-oxaloacetic transaminase: 289 mg/dL, serum
glutamic-pyruvic transaminase: 699 mg/dL, alkaline
phosphatase (ALP): 400 mg/dL] with a prolonged prothrombin
time, high gamma-glutamyltransferase and low albumin.
(3.2 mg/dL-corrected for hypoalbuminemia),raised
(1.2 mg/dL). Total bilirubin (TB) was grossly deranged
(DB) (9.2 mg/dL). Liver enzymes were deranged [serum
We present this rare occurrence of a 17 yr old boy, a known case of congenital hypoparathyroidism,
who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic
seizures. Premorbidly patient was on regular oral calcium supplementations with normal serum
calcium levels. Investigations revealed severe hypocalcaemia (3.2 mg/dL), low 25 hydroxyvitamin
D levels and hypomagnesaemia. The marked elevation of serum bilirubin was accompanied by
derangement of liver enzymes. Microbiological investigations were confirmatory for both hepatitis
A and typhoid fever. In spite of the aggressive management with intravenous calcium gluconate
infusion, refractory hypocalcaemia persisted with recovery only after gradual decline in the
bilirubin levels. We inferred that the cholestatic process produced by both acute viral hepatitis
A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well
Suman S Karanth et al./Asian Pacific Journal of Tropical Medicine (2012)667-668
25 hydroxyvitamin D levels were low. Microbiological
investigations revealed a positive anti hepatitis A virus
surface antigen and hepatitis C virus. He also tested negative
for antibodies to HIV. Widal test was positive with titres of
O: 1: 320 , H : 640. Serial blood cultures grew Salmonella
typhi. Patient was started on parenteral ceftriaxone. In view
of severe hypocalcemia, parenteral calcium gluconate was
administered immediately along with oral correction with
calcium supplements, calcitriol and magnesium. By day
2 of admission the hypomagnesemia was corrected with
no improvement in the serum calcium levels. Inspite of
aggressive management, serial calcium levels remained low
with persistence of carpopedal spams. On Day 4, TB peaked
to 20 mg/dL with a DB of 14 mg/dL and calcium levels being
the lowest (corrected value 3.0 mg/dL). By day 7, there was
a gradual decline in bilirubin and ALP levels which was
accompanied by a steady rise in the calcium levels. Day 8
onwards the patient was gradually weaned off the parenteral
calcium therapy gradually. By day 11 the parenteral
therapy was stopped and the patient was continued on both
oral calcium and calcitriol at a high dose which was also
gradually tapered. Antibiotic therapy was continued for a 14
day period. Clinically, the patient recovered completely with
normalization of the liver enzymes and prothrombin by day
15 and he was discharged with the premorbid dose of oral
(HAV) of IgM class but negative to antibodies for hepatitis B
Congenital hypoparathyroidism is either autoimmune or
due to genetic mutations in either the parathyroid hormone
or mitochondrial DNA. Hypoparathyroidism is diagnosed
when the intact PTH level is normal or inappropriately
low after ruling out hypomagnesemia. Serum phosphorus
levels are usually high. The resultant hypocalcemia
can present as asymptomatic in mild cases to acute life-
threatening crisis in severe cases. Abnormalities in levels
of vitamin D also contribute to hypocalcemia. The role
of 1, 25-dihydroxyvitamin D is to enhance the intestinal
absorption of both calcium and phosphorus[5,6]. Inadequate
vitamin D levels can lead to 50% reduction in intestinal
calcium absorption. This leads to only 10%-15% of dietary
calcium being absorbed. As our patient was a previously
worked up case of congenital hypoparathyroidism, we did
not investigate it further. In view of persistent hypocalcemia
despite aggressive therapy, we suspected a coexisting
vitamin D deficiency. At this admission, we found a
previously normal 25 hydroxy vitamin D level to be low.
In adults, hepatitis A is often symptomatic with rare
occurrence of fulminant form. The disease severity varies
with pre-disposing host factors, such as increased age or
existence of an underlying chronic liver disease. Atypical
clinical presentations like prolonged hepatitis, cholestatic
hepatitis and relapsing hepatitis though rare are known to
occur with hepatitis A infection.Typhoid fever, similar to
hepatitis A causes mild hepatitis and persistent fever[9,10].
There are a few case reports of severe cholestasis following
both acute hepatitis A infection and typhoid fever[2,11,12].
Studies on the impact of viral hepatitis on vitamin D levels
though limited, have shown to produce a steady decline in
(PTH) genes, calcium sensing receptors , transcription factors
vitamin D levels.
We ventured into the hypothesis that the cholestatic
process caused by this dual infection resulted in low 25
hydroxy vitamin D levels and a subsequent decreased
absorption of calcium, precipating this state of refractory
hypocalcemia. This was justified by observing lowest serum
calcium levels corresponding to the peak bilirubin levels.
A gradual improvement in the serum calcium levels which
paralled the steady fall in bilirubin levels supports the
hypothesis. At discharge, we were able to send the patient
on his premorbid dose of oral calcium. At subsequent
follow up, patient was better. To our best knowledge, this
is the first case report of severe refractory hypocalcemia
due to absorptive defects caused by simultaneous infection
with both enteric fever and hepatitis A. Though such a
phenomenon of absorptive defects is known, its clinical
implications are underestimated. This may land a clinician
in a therapeutic predicament. Clinicians need to be aware of
this for a prompt diagnosis and appropriate therapy.
Conflict of interest statement
We declare that we have no conflict of interest.
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