Dilated cardiomyopathy and cardiogenic shock in a toddler with vitamin D deficiency: a case report

Abstract

Vitamin D deficiency is a common nutritional problem in exclusively breastfed infants. Dilated cardiomyopathy is a rare but potentially fatal complication of this condition. We describe a 15-month-old who presented with cardiogenic shock. Laboratory and radiographic findings were consistent with vitamin D deficiency. Metabolic parameters normalised within one week and echocardiography normalised by 19 months after supplementation. Although rare, severe vitamin D deficiency must be on the differential for young children presenting with new-onset dilated cardiomyopathy. Clinicians must maintain a high index of suspicion for vitamin D deficiency in at-risk populations to prevent potentially life-threatening complications.

Introduction

Vitamin D deficiency is a common health concern among infants. It can result from maternal vitamin D deficiency during pregnancy, exclusive breastfeeding without supplementation, increased skin pigmentation, limited sun exposure, malabsorption disorders, and certain medications. ¹ Nutritional factors, particularly the lack of vitamin D supplementation in breastfed infants with darker skin, account for the majority of cases. ¹ Although typically associated with tetany and seizures, vitamin D deficiency has also been linked to dilated cardiomyopathy. ^2–8 In this report, we describe the case of a 15-month-old with dilated cardiomyopathy, vitamin D deficiency rickets and hypocalcaemia.

Case

An exclusively breastfed 15-month-old African-American male presented to the emergency department in cardiogenic shock with fussiness, hypoactivity, and decreased oral intake. During evaluation, he suffered a cardiac arrest and status epilepticus. Initial echocardiogram demonstrated a severely dilated left ventricle with end diastolic dimension of 36.5 mm (z score + 3.4), severely diminished left ventricular systolic function with left ventricular ejection fraction of 31%, and shortening fraction of 14%. Brain natriuretic peptide was elevated to 1106 pg/mL. Initial electrocardiogram was notable for QTc of 518 msec, PR interval of 132 msec, and T wave inversions. He was subsequently admitted to the cardiac ICU for inotropic support.

Laboratory testing was notable for a 25-hydroxy vitamin D level (25-OH) less than the detectable limit (<3.4 ng/mL) and severe hypocalcaemia with an ionised calcium of 0.64 mmol/L and a serum calcium of 6.24 mg/dL. While his phosphorus and magnesium levels were normal, his alkaline phosphatase and parathyroid hormone were highly elevated at 1708 U/L and 619 pg/mL, respectively. Genetic testing, including fluorescence in situ hybridisation for DiGeorge Syndrome and rapid exome sequence analysis, was normal. Skeletal survey showed diffuse cupping and fraying of the metaphysis of his long bones suggestive of rickets. On his physical exam, frontal bossing, a positive Chvostek sign, widening wrists, and inflammation of the costochondral junction were noted. Aside from severe hypocalcaemia, routine diagnostic testing for other aetiologies of dilated cardiomyopathy, including viral titres and testing for inherited causes of cardiomyopathy, was negative.

He was treated initially with intravenous calcium gluconate (64 mg elemental calcium/kg/day) and ergocalciferol (50,000 IU daily). He demonstrated significant clinical improvement from a cardiovascular standpoint with this combination, suggesting a diagnosis of vitamin D deficiency-associated cardiomyopathy. Eventually, he was transitioned to oral calcium carbonate (45 mg/kg/day of elemental calcium) once he was stable. He achieved normocalcaemia and sufficient 25-OH levels after seven days of aggressive treatment with downtrending alkaline phosphatase and parathyroid levels. His most recent echocardiogram at 19 months post-diagnosis demonstrated complete recovery of left ventricular systolic function (ejection fraction of 70% and shortening fraction of 39%) with resolution of left ventricular dilation (end diastolic dimension of 3.52 cm, z-score + 1.2).

Discussion

Vitamin D is a fat-soluble vitamin essential for bone metabolism and calcium homeostasis. It can be synthesised after sunlight exposure or absorbed from the diet or supplements. Maternal vitamin D deficiency during pregnancy, exclusive breastfeeding without supplementation, skin pigmentation, decreased sun exposure, malabsorption, and certain medications can all lead to vitamin D deficiency. ¹ Hypocalcaemia secondary to calcipenic rickets is an uncommon but known aetiology of dilated cardiomyopathy. ^2–8 Calcium release from the sarcoplasmic reticulum is essential for cardiac muscle contraction and inadequate levels may impair cardiac contractility and precipitate, or worsen, existing heart failure. ⁹

In the United States, we are aware of only three similar reports. Two were individual case reports from 2003 and 2007. ^2,3 The last was a single centre case series of four patients from 2009. ⁴ In each of these cases, the patients were African-American, breastfed, and between 4 and 10 months of age when diagnosed. This is consistent with a systematic review from 2013, which found a mean age of diagnosis of 5 months. ⁵ While our patient was also African-American and exclusively breastfed, he was significantly older at 15 months of age. We could only find two other case reports of a toddler developing this condition in the past 50 years; one being a 14-month-old from Turkey in 2007 and the other a 15-month-old child from India in 2011. ^6,7 In all three cases, there was prolonged breastfeeding with failure to provide vitamin D supplementation or introduce solid foods.

The clinical presentation of rickets-associated cardiomyopathy is variable, ranging from tachypnoea and cardiomegaly to cardiogenic shock requiring extracorporeal membrane oxygenation. ⁵ In our case, the patient suffered a cardiac arrest after presenting in cardiogenic shock and required inotropic support while initiating treatment with calcium supplementation. Another unique feature that is inconsistently present in described cases is electrocardiogram changes, including prolonged PR interval, prolonged QTc, and T wave changes. ⁸ In our patient, the first electrocardiogram was notable for QTc prolongation and T wave abnormalities, which resolved by the time of discharge. However, it is worth noting that these changes can also occur in the setting of sick myocardium and typically resolve over time as the patient clinically improves. Although the prognosis for dilated cardiomyopathy is often poor, the outcome of calcipenic rickets-induced cardiomyopathy is typically quite favourable with an 8.5% incidence of mortality in a systematic review. ⁵ The average time for systolic ventricular function to normalise is 12 months; however, it may take up to 28 months for complete recovery after diagnosis. ⁴ In our case, the patient demonstrated normal systolic function by 19 months post diagnosis.

Vitamin D deficiency is an underrecognized condition with an increased prevalence of nutritional rickets in exclusively breastfed infants over the last few years. ² Current American Academy of Pediatrics guidelines recommend 400 IU/day of vitamin D for all exclusively breastfed infants. ¹⁰ Because of the potential life-threatening implications, routine supplementation, early recognition, and prompt correction of hypocalcaemia are paramount.

Vitamin D deficiency should be considered as a possible aetiology of dilated cardiomyopathy in any exclusively breastfed infant as it is easily treatable with an excellent prognosis.