Key Words:
Hypocalcemia , Dilated Cardiomyopathy, Vitamin D Deficiency
Abstract
Hypocalcaemia is a rare but reversible cause of dilated
cardiomyopathy with limited cases being reported in the
literature. Vitamin D deficiency is the main cause of
hypocalcaemia in almost all reported cases. We report a
newborn who presented with hypocalcaemia induced dilated
cardiomyopathy secondary to Vitamin D deficiency. After
calcium therapy, the baby showed a rapid recovery of the
cardiac function.
Introduction
Dilated cardiomyopathy (DCM) has an estimated incidence of
1.13 cases per 100,000 children. Diagnosing the primary
etiology occurs in fewer than half of these children but
significantly improves their outcome [1]. DCM is mostly
idiopathic, however infection and metabolic causes haves been
identified in some cases in which the defect in myocardial
contractility is irreversible [2]. Here we report a case
of dilated cardiomyopathy secondary to hypocalcaemia that
occurred due to Vitamin D deficiency in an infant.
Case Report
An exclusively breastfed male child with a birth weight of
3.20 kilograms, who had a term delivery by LSCS and discharged
on the third day of life after an uneventful post natal
period, presented to us at the age of 53 days with poor
feeding, shortness of breath and sweating of 3 days duration.
On examination he had tachycardia (PR 166/minute) and
tachypnoea (RR 68/minute) with cold extremities (CRT > 3
seconds). All the peripheral pulses were felt with no
radio-femoral delay. The O2 saturation was less than 90% in
room air but improved to 100% with inhalation of 5 liter
oxygen/min. The infant's weight was 5.5 Kg, length 58 cm, and
head circumference 38 cm, all within the normal range.
Examination of the cardio-vascular system revealed that the
apex was in the sixth left intercostal space in the
mid-clavicular line. Auscultation revealed a loud third heart
sound and a gallop rhythm with normal first and second heart
sounds. On auscultation of the respiratory system there were
bilateral crackles. Examination of the abdomen revealed a
liver enlargement with a span of 9 cms.
Three hours after admission the infant had a generalized tonic
seizure and went into apnoea with bradycardia, which was
promptly managed and resuscitated with bag and mask
ventilation.
The infant's initial investigation reports were as follows:
Random Blood sugar: 198 mg%, Serum Calcium: 5 mg%, Serum
Phosphates: 8.8mg%, Serum Alkaline phosphatase: 475 IU/litre,
Blood Urea: 27 mg%, Serum Creatinine: 0.4 mg%, Serum
Magnesium: 2.1 mg%, Serum electrolytes and Complete Blood
Counts were within the normal ranges.
Chest X-Ray showed cardiomegaly (CT ratio of 65%) with clear
lung fields and Electrocardiography showed prolonged QT
interval with ST segment prolongation. ECHO showed depressed
left ventricular function and ejection fraction was only 41%.
The impression given by the cardiologist was Dilated
Cardiomyopathy (DCM) with possibility of myocarditis.
The infant was managed with oxygen, intravenous fluids,
intravenous anti-convulsants (Lorazepam followed by
Fosphenytoin) and anti-biotics (Co-amoxyclav) initially.
Intravenous Calcium gluconate was given as bolus followed by a
continuous infusion after getting the serum calcium results.
Even after 3 days of Calcium infusion the serum Calcium was
still low (7.5mg%). In the meantime his Serum Vitamin D levels
were obtained. Serum 1,25-di-hydroxy-cholecalciferol was 53
pmol/litre (normal) but Serum 25-hydroxy-cholecalceferol was
low at 13.4 (normal: 30.0 to 74.0 ng/mL), and he had a raised
Serum Parathyroid hormone level of 140.80 pg/ml (normal being
15.0 - 68.0 pg/ml). The infant's mother's Vitamin D level was
within normal limits.
A diagnosis of Vitamin D deficiency was made and Injection
Cholecalciferol followed by oral 1,25
di-hydroxy-cholecalciferol was given daily. He gradually
improved, his serum Calcium level normalized and his ECHO
showed an improved left ventricular ejection fraction of 71%
with improved left ventricular contractility. He was
discharged on the 12th day of admission, on oral calcium
supplement. The infant is now 6 months old, completely
asymptomatic, on maintenance dose of calcium orally and has
normal growth and development.
Discussion
Calcium has a central role in myocardial contraction coupling
and hypocalcaemia reduces the myocardial function. Congestive
cardiac failure due to hypocalcaemia have been reported,
though rare and only few cases of hypocalcaemia induced
cardiomyopathy have been reported [3,4].
Hypocalcaemia causing DCM is reversible with complete recovery
after normalization of serum calcium is seen. Vitamin D
deficiency is the main cause of hypocalcaemia in infants and
older children. Nutritional rickets is still prevalent with
the primary etiology being Vitamin-D deficiency in breastfed
infants and children [1,5].
Ionized Calcium has a central role in regulating myocardial
contraction. During the activation of cardiac action
potential, ionized calcium enters the cell through
depolarization activated calcium channels. Plasma membrane
(PM) depolarization triggers the opening of voltage-gated Ca2+
channels (VGCC), allowing influx of calcium ions. This
triggers the release of a greater amount of Ca2+ from the
sarcoplasmic reticulum (SR) via ryanodine receptors (RyR2).
After Ca2+ - induced contraction of the sarcomere, myocyte
relaxation occurs when calcium ions are pumped back into the
SR by sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) or
removed from the myocyte by the Na+/Ca2+ exchanger (NCX) [6].
In immature heart, this SR calcium transport system is less
well developed and such hearts consequently have an increased
dependence on transport of calcium from outside the cell for
contraction [7].
Vitamin D deficiency remains a major public health problem in
India especially among infants who are exclusively breastfed
and born to mothers with high-risk factors such as low Vitamin
D stores, dark skinned and or living a sedentary life style
that further limit adequate ultraviolet light exposure [8-10].
Infants born to mothers with deficiency of Vitamin D are at
risk of developing early and fatal sequelae of hypocalcaemic
Vitamin D deficiency [11-13].
In a study where a hospital database search was conducted from
the year 1997 to 2007 to identify patients with confirmed
Vitamin D deficiency in addition to DCM, four exclusively
breastfed African American infants were identified. These
infants presented with congestive heart failure secondary to
DCM and on admission they were found to have laboratory
evidence consistent with hypocalcaemic rickets. These patients
responded dramatically to treatment with Vitamin D and Calcium
and cardiac functions returned to normal within months [11].
In another study, 15 Indian infants (age between 45 days and 5
months) presented with severe left ventricular dysfunction,
and were found to have hypocalcaemia with or without
hypomagnesaemia. Vitamin D was identified as the main cause of
hypocalcaemia. These children improved on supplementation of
Vitamin D and Calcium [14].
In our case, the baby presented with severe hypocalcaemic DCM
at a very young age of one and half months. He was exclusively
breastfed. Our baby was investigated for other possible causes
for his DCM; like metabolic disorders, viral infections and
other cardiac causes leading to DCM. There was no family
history of any similar problem and the investigations were
negative for other causes, hence it was evident that it was
only due to Vitamin D deficiency. The child also improved very
well with Calcium and Vitamin D administration. Most cases of
nutritional rickets can be prevented by universal
administration of daily multivitamin containing 400 IU of
Vitamin D to infants who are breast fed; older children should
receive 600 IU/ day [15].
Conclusion
The association of hypocalcemia-induced DCM is of noted
importance when encountering a patient with a new diagnosis of
DCM. With increased suspicion, the diagnosis of
hypocalcemia-induced DCM can be made and prompt treatment can
lead to recovery of cardiac function and better patient
outcome. This report adds to the already existing evidence
that Vitamin D deficiency remains a major health problem in
India. It highlights the importance of administering Vitamin D
prophylaxis for pregnant mothers at a daily dose of 800 - 1000
units and for babies at a daily dose of 400 units soon after
birth. This can prevent hypocalcemia-induced cardiac problems
which is a serious complication of nutritional vitamin D
deficiency.
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