Introduction

Dilated cardiomyopathy (DCM) is an important cause of heart failure in children. The most common causes of DCM are idiopathic, familial and acute myocarditis. Additionally, viral infections as well as endocrine and metabolic diseases may cause DCM (1). In DCM, treatment of which usually requires transplantation, medical therapy rarely results in complete improvement. There are studies suggesting that vitamin D deficiency is also a treatable cause of DCM (2). Herein, we present a case who was followed-up with the diagnosis of DCM and in whom regression of heart failure symptoms with vitamin D therapy was observed.

Case report

A 3-month-old boy who was being followed-up in Pediatric Cardiology Clinic due to DCM was referred to Pediatric Endocrinology Outpatient Clinic in Sanliurfa Harran University Hospital due to low serum calcium (Ca) level. His parents were first-degree relatives. The patient was born mature with a weight of 3.200 g via spontaneous vaginal delivery to a mother with Hashimoto’s thyroiditis. He was referred to the Pediatric Cardiology Clinic of Gaziantep University due to heart murmur. Echocardiography (ECHO) revealed remarkably dilated left ventricle, hypokinetic myocardium, and septal deviation to the right, trace mitral insufficiency, decreased systolic function, an ejection fraction (EF) of 42%, and a fractional shortening (FS) by 20%. In further analysis performed for DCM, serologic tests (hepatitis, Epstein-Barr virus, and available viral analyses) were determined to be negative, and urine and blood amino acids, tandem-mass spectrometry findings and serum carnitine levels were normal. The patient was diagnosed with DCM and started on digoxin and angiotensin-converting-enzyme inhibitor. Additionally, treatment for iron deficiency anemia was initiated. On his physical examination, height was 59.5 cm (50th percentile) and body weight was 6.300 g (50-75th percentile). In addition, significant third degree heart murmur, tachycardia, widened wrists, and large anterior fontanel were remarkable. Results of laboratory analysis for rickets revealed a Ca level of 6.8 mg/dL, phosphorus level of 4.9 mg/dL, alkaline phosphatase level of 1637 U/L, parathyroid hormone (PTH) level of 191.2 pg/mL, and 25-hydroxyvitamin D level of 5.7 ng/mL. Vitamin D level of the mother was 12 ng/mL. Telecardiogram showed an increased cardiothoracic ratio and rachitic changes at the costochondral junction (Figure 1). Signs consistent with rickets were also remarkable on the hand-wrist radiograph (Figure 2). The patient initially received Ca lactate therapy and then vitamin D therapy due to rickets associated with Vitamin D deficiency. At the 3rd month of the therapy, laboratory tests returned to normal. In addition, radiological signs of rickets disappeared and echocardiographic findings returned to normal. Table 1 summarizes laboratory and ECHO findings of the patient before and after the therapy. Digoxin was discontinued. Since cardiac functions began to improve after the therapy, DCM associated with vitamin D deficiency was considered in the patient.

Discussion

Herein, a 3-month-old boy whose cardiac functions dramatically improved after Ca and vitamin D therapies was presented. Ca is of great importance for cardiac function. Vitamin D is a key vitamin for bone metabolism and its deficiency usually results from inadequate exposure to sunlight. Vitamin D deficiency may also be due to poor nutrition, malabsorption syndromes, and renal diseases. Vitamin D receptor (VDR) is found in almost all cells. Heart and blood vessels where VDR and 1-α-hydroxylase are expressed are target organs for vitamin D. VDR activation enhance the intracellular transport of Ca; thus, relaxation of cardiomyocytes is accelerated and diastolic functions are improved. Moreover, development of cardiac muscle hypertrophy has been detected in VDR knockout mice, and it has been demonstrated that calcitriol reverses cardiomyocytes hypertrophy (3). Vitamin D deficiency has been found to have unfavorable effects on heart not only due to Ca but also due to PTH. It has been reported that increased PTH level secondary to vitamin D deficiency enhances cardiovascular diseases and mortality. PTH has been shown to increase blood pressure and induce myocardial hypertrophy and proarrhythmic effects (4). Many pediatric DCM cases with vitamin D deficiency that showed improvement with treatment have been reported in the literature. The first case was reported in 1983 in Spain; and the term “rachitic DCM” was introduced to describe this situation (5). Since then more than 50 children with rachitic DCM have been reported. Although case reports are more frequent in the literature, an increase was observed in case series in the recent years due to increase in awareness about the relation between DCM and vitamin D deficiency. In the first and the largest series from England, hypocalcaemia and rickets were found in retrospective analysis of 16 cases with DCM over a period of 6 years of whom six died of heart failure and 10 completely improved (6). A study from the USA found rickets in four of 47 infants with DCM in a 10-year period and reported that cardiac functions dramatically improved with treatment (7). In a study which conducted in India, hypocalcaemia was determined in 15 (mean age, 2 months) of 94 cases with left ventricular dysfunction in a 7-year period (8). Twelve had signs of congestive heart failure and three had cardiogenic shock. While 14 cases showed complete improvement, one case died due to recurrent hypocalcaemia. To date, there are two cases reported from Turkey. One of them was a 9-month-old girl (9), and the other one was a 15-month-old boy, who was reported from our region 5 years ago and showed complete improvement with treatment (10). Sanliurfa province is located in a region where annual exposure to sunlight is high. However, vitamin D deficiency may be encountered in infants due to the mothers’ low exposure to sunlight and poor nutrition. Vitamin D deficiency-related heart failure is encountered not only in children but also in adults. In the literature, there are reported cases with hypoparathyroidism due to complication of thyroid surgery who presented with heart failure that resolved vitamin D therapy (11). In conclusion, vitamin D deficiency should be considered during etiological evaluation of DCM in the regions that are endemic for nutritional rickets, and it should be kept in mind that vitamin D therapy may provide dramatic improvement in cardiac functions. Ethics Informed Consent: Consent form was filled out by all participants. Authorship Contributions Surgical and Medical Practices: Bülent Koca, Erdal Eren, Osman Baspinar, Concept: Mahmut Abuhandan, Design: Mahmut Abuhandan, Erdal Eren, Data Collection or Processing: Erdal Eren, Bülent Güzel, Analysis or Interpretation: Erdal Eren, Osman Baspinar, Literature Search: Erdal Eren, Bülent Güzel, Writing: Erdal Eren, Conflict of Interest: No conflict of interest was declared by the authors, Financial Disclosure: The authors declared that this study has received no financial support, Peer-review: Internal peer-reviewed.