Hypertrophic Dilated Cardiomyopathy Research Articles

Evaluating convolutional neural network-enhanced electrocardiography for hypertrophic cardiomyopathy detection in a specialized cardiovascular setting.

The efficacy of convolutional neural network (CNN)-enhanced electrocardiography (ECG) in detecting hypertrophic cardiomyopathy (HCM) and dilated HCM (dHCM) remains uncertain in real-world applications. This retrospective study analyzed data from 19,170 patients (including 140 HCM or dHCM) in the Shinken Database (2010-2017). We evaluated the sensitivity, positive predictive rate (PPR), and F1 score of CNN-enhanced ECG in a ''basic diagnosis'' model (total disease label) and a ''comprehensive diagnosis'' model (including disease subtypes). Using all-lead ECG in the "basic diagnosis" model, we observed a sensitivity of 76%, PPR of 2.9%, and F1 score of 0.056. These metrics improved in cases with a diagnostic probability of ≥ 0.9 and left ventricular hypertrophy (LVH) on ECG: 100% sensitivity, 8.6% PPR, and 0.158 F1 score. The ''comprehensive diagnosis'' model further enhanced these figures to 100%, 13.0%, and 0.230, respectively. Performance was broadly consistent across CNN models using different lead configurations, particularly when including leads viewing the lateral walls. While the precision of CNN models in detecting HCM or dHCM in real-world settings is initially low, it improves by targeting specific patient groups and integrating disease subtype models. The use of ECGs with fewer leads, especially those involving the lateral walls, appears comparably effective.

Abstract P1171: Golgi Localized DHHC3 And DHHC7 Contribute To The Initiation Of The Cardiac Hypertrophy Response In Vivo

Lipid modifications provide a layer of control over cardiac signaling molecules, including small GTPases and heterotrimeric G-proteins. Lipidation of signaling factors often permits their preferential localization to intracellular membranes and organelles where they then activate downstream effectors. S-palmitoylation is a reversible lipid modification catalyzed by a family of 23 palmitoyl acyltransferases, which are characterized by a conserved zinc finger-like aspartate-histidine-histidine-cystine (zDHHC) domain. Although the importance of GTPase palmitoylation is appreciated, our understanding of enzyme-substrate specificity remains uncertain and how these enzymes regulate cardiac stress signaling and hypertrophy is unknown. To examine the roles of the cardiac-expressed zDHHCs, we overexpressed zDHHC3, 5, 6, 7 and 13 using adeno-associated viruses. Overexpression of membrane-localized zDHHC5, ER localized zDHHC6 or Golgi-localized zDHHC13 had no effect on cardiac function, while overexpression of zDHHC3 or zDHHC7 (both Golgi-localized) caused dilated hypertrophic cardiomyopathy. zDHHC3 and zDHHC7 expression were also upregulated in the heart in response to transverse aortic constriction. To gain a better understanding of the physiological role of zDHHC3 and zDHHC7 in the heart we utilized gene-deleted mice subjected to models of pathological hypertrophy. At baseline, neither single (zDHHC3 and zDHHC7) or double (zDHHC3/7) knockout mice exhibit alterations in cardiac function. Total levels of GTPase signaling proteins are unchanged, although both single and double knockout mice have reduced palmitoylation of Gαs and Rac1. In response to pressure overload, knockout of both zDHHC3/7 delayed hypertrophic progression at an early timepoint (1 week), although the response is unchanged at a late timepoint (8 weeks). We conclude that both zDHHC3 and 7 contribute to the initiation of cardiac hypertrophy but are not key regulators of hypertrophic signaling.

Myocardial perfusion findings evaluated by gated-SPECT in dyslipidemic very high-risk patients

Abstract Funding Acknowledgements Type of funding sources: None. Background. Dyslipidemia is one of the main risk factors for atherosclerotic disease. Timely diagnosis and appropriate treatment are therefore essential in the prevention and recurrence of cardiovascular disease (CVD). The detection of ischemia with myocardial perfusion gated-SPECT is a valuable diagnostic option that provides complete information to select the best therapeutic option, reducing morbidity and mortality in this group of patients. Purpose. To evaluate the findings of myocardial perfusion imaging (MPI) using gated-SPECT in a group of patients with dyslipidemia and very high cardiovascular risk. Methods. We retrospectively evaluated gated-SPECT results of 66 very high-risk dyslipidemic patients with a diagnosis or clinical suspicion of coronary artery disease (CAD). Exclusion criteria: structural heart disease, dilated hypertrophic cardiomyopathy, hemodynamic instability, low-intermediate risk. Rest-stress imaging with gated-SPECT Technetium-99m Sestamibi was acquired on a dedicated cardio gamma camera and subjectively evaluated in a 17-segment analysis. Ischemia was classified as mild, moderate, and severe. Statistical analysis: SPSS system, continuous data were expressed as mean ± SD, percentages were rounded; Chi-square and Student’s t-tests were used. Results. Mean age 61.06 ± 12.87 years old, 40 (61%) were men; 61 (92%) with primary and 5 (8%) with familial hypercholesterolemia. More than 80% have at least one or more cardiovascular (CV) risk factors; 73% have dyslipidemia, diabetes, and arterial hypertension, 52% tabaquism, 36% obesity, 11% kidney disease, and 30% family history of CV disease; all women were post-menopausal (44%). Asymptomatic (56%), 30% with dyspnea or equivalents, 9% atypical chest pain, and 5% typical angina. Gated-SPECT: 56% with ischemia; mild ischemia was present in 33% and 11% of men and women, and moderate in 35% and 27% respectively. Primary hypercholesterolemia: 26 % with mild, 28% moderate, and 46% without ischemia; 80% of familial hypercholesterolemia with moderate and 20% without ischemia. Conclusion. Myocardial ischemia was present in 56% of very high-risk dyslipidemic patients, predominantly in men (67.5%). Although 56% were asymptomatic, ischemia was detected in 54% of the patients with primary and 80% with familial hypercholesterolemia. It is advisable to perform MPI with gated-SPECT for the early detection of ischemia in high-risk dyslipidemic patients, even asymptomatic.

Mitochondrial Fatty Acid Oxidation Disorders Associated with Short-Chain Enoyl-CoA Hydratase (ECHS1) Deficiency.

Mitochondrial fatty acid β-oxidation (FAO) is the primary pathway for fatty acid metabolism in humans, performing a key role in liver, heart and skeletal muscle energy homeostasis. FAO is particularly important during times of fasting when glucose supply is limited, providing energy for many organs and tissues, including the heart, liver and brain. Deficiencies in FAO can cause life-threatening metabolic disorders in early childhood that present with liver dysfunction, hypoglycemia, dilated hypertrophic cardiomyopathy and Reye-like Syndrome. Alternatively, FAO defects can also cause ‘milder’ adult-onset disease with exercise-induced myopathy and rhabdomyolysis. Short-chain enoyl-CoA hydratase (ECHS1) is a key FAO enzyme involved in the metabolism of fatty acyl-CoA esters. ECHS1 deficiency (ECHS1D) also causes human disease; however, the clinical manifestation is unlike most other FAO disorders. ECHS1D patients commonly present with Leigh syndrome, a lethal form of subacute necrotizing encephalomyelopathy traditionally associated with defects in oxidative phosphorylation (OXPHOS). In this article, we review the clinical, biochemical and genetic features of the ESHS1D patients described to date, and discuss the significance of the secondary OXPHOS defects associated with ECHS1D and their contribution to overall disease pathogenesis.

Evaluation of right ventricular function using liver stiffness in patients with left ventricular assist device.

OBJECTIVES: Although right ventricular failure (RVF) is a major concern after left ventricular assist device (LVAD) implantation, methodologies to evaluate RV function remain limited. Liver stiffness (LS), which is closely related to right-sided filling pressure and may indicate RVF severity, could be non-invasively and repeatedly assessed using transient elastography. Here we investigated the suitability of LS as a parameter of RV function in pre- and post-LVAD periods. METHODS: The study included 55 patients with LVAD implantation as a bridge to transplantation between 2011 and 2015 whose LS was assessed using transient elastography. RESULTS: Seventeen patients presented with RVF, defined as requiring inotropic support for ≥30 days, nitric oxygen inhalation for ≥5 days, and/or mechanical RV support following LVAD implantation. Survival of patients with RVF was significantly worse compared with that of patients without RVF. Multivariate logistic regression analysis identified preoperative LS, LV diastolic dimension, RV stroke work index, and dilated phase of hypertrophic cardiomyopathy aetiology as significant risk factors; the combination of these parameters could improve predictive power of post-LVAD RVF with areas under the curve of 0.89. Furthermore, LS was significantly decreased by LV unloading and significantly correlated with right-sided filling pressure. CONCLUSIONS: In addition to dilated hypertrophic cardiomyopathy aetiology, reduced RV stroke work index and small LV dimension, we demonstrated that non-invasively measured LS was a predictor of post-LVAD RVF and can be used as a parameter for the evaluation and optimization of RV function in the perioperative period.

Clinical characteristics and outcome of patients with dilated-hypertrophic cardiomyopathy

To define the clinical characteristics and outcome of patients with dilated-hypertrophic cardiomyopathy (D-HCM). Clinical data of HCM patients hospitalized from January 2002 to December 2015 in our hospital were retrospectively analyzed. Patients were divided into D-HCM and classic HCM patients. The D-HCM patients were followed up by phone. A total of 616 consecutive HCM patients were evaluated. Twenty one patients (3.4%) were diagnosed with D-HCM (average age(58.8±10.4) years, 13 males). It took (14.2±7.1)years for classic HCM patients to develop D-HCM. Compared to classic HCM patients, D-HCM patients were younger at the time of first HCM diagnosis ((39.7±10.4) years old vs. (48.5±9.5) years old, P<0.001) and had higher ratio of sudden cardiac death family history (19.0%(4/21) vs. 2.5%(14/558), P=0.003), more patients of future D-HCM patients had ventricular tachycardia (38.1%(8/21) vs. 5.7%(32/558), P<0.001) and higher Troponin-I(66.7%(14/21) vs. 9.3%(52/558), P<0.001) before the left ventricular cavity enlargement. Moreover, MLVWH ((24.8±4.2) mm vs. (17.2±3.5) mm, P<0.001) was significantly thicker and LAD ((39.8±5.9) mm vs. (35.2±3.3) mm, P<0.001) was significantly larger in D-HCM patients than in classical HCM patients. During the(3.8±1.9) years follow up period, 12 out of 21 D-HCM patients died (57.1%), 5 cases(23.8%)died of severe heart failure and 7 cases(33.3%) died of sudden cardiac death. One patient received heart transplantation. Few classical HCM patients progressed into D-HCM in this cohort. Patients diagnosed as HCM at young age, HCM patients with abnormal Troponin I and ventricular tachycardia are at higher risk of developing D-HCM. The prognosis of D-HCM is very poor, and heart failure and sudden cardiac death are the main causes of death.

Large Thrombus Originating From Left Atrial Diverticulum

A 45-year-old man was admitted to our hospital for evaluation of a left atrial (LA) mass. The patient had a history of dilated hypertrophic cardiomyopathy, atrial fibrillation (AF), diabetes mellitus, and sustained ventricular tachycardia that was treated by implantation of a cardioverter-defibrillator. He had developed AF 1 year earlier and was followed up at the outpatient clinic. He had been treated with warfarin at a dose that resulted in an international normalized ratio of 2.0 to 3.0. The LA mass was detected incidentally on routine transthoracic echocardiography. He was referred to our hospital because the size of the LA mass was unchanged after intensive anticoagulation with intravenous heparin infusion. The mobile LA mass along the interatrial septum was detected by transthoracic echocardiography in the apical 4-chamber view (Figure 1 and Movie I in the online-only Data Supplement). Transesophageal echocardiography showed a huge mobile mass (2.6×1.4 cm) originating from the roof of the LA (Figure 2A and Movie II in the online-only …

Mitochondrial cardiomyopathies: how to identify candidate pathogenic mutations by mitochondrial DNA sequencing, MITOMASTER and phylogeny

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. Owing to a high mutation rate, mtDNA defects may occur at any nucleotide in its 16 569 bp sequence. Complete mtDNA sequencing may detect pathogenic mutations, which can be difficult to interpret because of normal ethnic/geographic-associated haplogroup variation. Our goal is to show how to identify candidate mtDNA mutations by sorting out polymorphisms using readily available online tools. The purpose of this approach is to help investigators in prioritizing mtDNA variants for functional analysis to establish pathogenicity. We analyzed complete mtDNA sequences from 29 Italian patients with mitochondrial cardiomyopathy or suspected disease. Using MITOMASTER and PhyloTree, we characterized 593 substitution variants by haplogroup and allele frequencies to identify all novel, non-haplogroup-associated variants. MITOMASTER permitted determination of each variant's location, amino acid change and evolutionary conservation. We found that 98% of variants were common or rare, haplogroup-associated variants, and thus unlikely to be primary cause in 80% of cases. Six variants were novel, non-haplogroup variants and thus possible contributors to disease etiology. Two with the greatest pathogenic potential were heteroplasmic, nonsynonymous variants: m.15132T>C in MT-CYB for a patient with hypertrophic dilated cardiomyopathy and m.6570G>T in MT-CO1 for a patient with myopathy. In summary, we have used our automated information system, MITOMASTER, to make a preliminary distinction between normal mtDNA variation and pathogenic mutations in patient samples; this fast and easy approach allowed us to select the variants for traditional analysis to establish pathogenicity.

BIN1 Localizes the L-Type Calcium Channel to Cardiac T-Tubules

Author SummaryCalcium plays a primary role in regulating heart function. During each heartbeat, calcium ions cross the membrane of individual cardiac muscle cells and trigger a rapid increase of calcium within the cell (called the calcium transient). Calcium causes the muscle cells to contract and determines the strength of the overall heartbeat. Each cardiac muscle cell has many small tubular-like membrane invaginations known as T-tubules where calcium channels localize, allowing calcium ions to enter and immediately encounter intracellular calcium release organelles. While this organization is well described, it is not known how calcium channels localize to T-tubule membrane. Here we show that in human and mouse heart cells, a membrane scaffolding protein known as BIN1 is localized together with calcium channels at T-tubules. Using high-resolution live cell microscopy, we found that microtubules, which are necessary for calcium channel delivery to the membrane, are also tethered by BIN1. Loss of BIN1 in cardiac cells impairs delivery of calcium channels to the membrane and diminishes the intracellular calcium transient. According to this model, microtubules function as highways that carry newly synthesized calcium channels to BIN1-containing membrane. Once tethered to T-tubules by BIN1, the microtubules can deliver their calcium channel cargo. We postulate that this calcium channel delivery pathway is important to the regulation of cardiac calcium signaling and beat-to-beat cardiac function.

Pallister–Killian syndrome in a girl with mild developmental delay and mosaicism for hexasomy 12p

We report on a 5-year-old girl with Pallister-Killian syndrome (OMIM #601803) due to mosaicism of two supernumerary isochromosomes (hexasomy 12p). Hexasomy 12p was found in 20% of the cells by chromosome analysis of cultured skin fibroblasts and confirmed by FISH- and arrayCGH analysis. The girl has woolly and sparse hair, absence of lateral eyebrows, dry skin, brittle nails, hypopigmented patches, frontal bossing, hearing loss, hypertrophic dilated cardiomyopathy, polydactyly, and mild developmental delay. This is the second live case of mosaicism for hexasomy 12p to be reported. A gene-dosage hypothesis has previously suggested that cases with hexasomy 12p would have a worse phenotype than cases with tetrasomy 12p. The relatively mild symptoms found in the current girl with hexasomy 12p may to contradict this hypothesis.

Abstract 4956: A Risk Stratification Analysis of Predictors of Death or Transplant in Children with Hypertrophic Cardiomyopathy

We previously reported initial results from a univariate analysis of baseline predictors of death or heart transplant in children with hypertrophic cardiomyopathy (HCM). We present here the final multivariate analysis resulting in risk stratification rules for 6 HCM etiologic subgroups in children. The Pediatric Cardiomyopathy Registry collected longitudinal data on 882 children with HCM from 1990 –2003. The primary outcome was the earlier of death or heart transplantation. Cox regression was used to identify the 3 most important risk factors at time of diagnosis for each HCM subgroup; all echo measures were expressed as z-scores. Multivariate analysis revealed that children with idiopathic HCM diagnosed by 1 year were at higher risk of poor outcome if they had CHF, low BSA, or elevated LV mass, while risk factors for children diagnosed after 1 year were female gender, depressed fractional shortening, and elevated wall thickness. Risk factors for children with malformation syndrome were Black race, CHF and increased wall thickness; Black race, younger age, and elevated LV mass for children with inborn errors of metabolism; younger age, CHF, and increased wall thickness for children with mixed restrictive HCM; and decreased weight, family history of heart disease, and increased wall thickness for children with mixed dilated HCM. Children with multiple risk factors present at diagnosis had a significantly worse prognosis compared to those with 0 or 1 risk factors. (Figure ) Based on etiologic subtype and number of risk factors present at diagnosis, clinicians can reliably estimate the risk of death of transplant in children with HCM.

Increased Brain Natriuretic Peptide Secretion is a Marker of Disease Progression in Nonobstructive Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is associated with increased plasma brain natriuretic peptide (BNP), but sequential plasma and myocardial BNP assessment in stable and dilated HCM has never been performed. Forty consecutive HCM patients (42 +/- 8 years, 25 males) underwent cardiac catheterization, angiography, and left ventricular (LV) endomyocardial biopsy. During follow-up (70.5 +/- 6.7 months), 30 patients (Group 1) remained stable whereas 10 patients (Group 2) progressed to dilated phase. Group 2 patients underwent a second invasive study with LV biopsy. BNP plasma levels were measured at baseline and at follow-up in all patients. All biopsies were processed for histology and immunohistochemistry with anti-BNP antibodies. BNP plasma levels remained unchanged in Group 1, whereas it significantly increased in all Group 2 patients who exhibited an elevation of LV and right ventricular end-diastolic pressure. Immunohistochemistry showed an increase of BNP-positive myocytes in follow-up biopsies when compared with baseline (75.0 +/- 15.0 % versus 29.8 +/- 10.0 %; P = .005) with a significant correlation with LV end-diastolic pressure (r = 0.78, P < .001) and plasma BNP (r = 0.83, P < .001). Progression to end-stage of HCM is characterized by further increase of myocardial and plasma BNP. Serial assessment of plasma BNP may provide noninvasive recognition of hemodynamic deterioration, allowing prompt institution of heart failure therapy.

Left ventricle restoration in patients with non-ischemic dilated cardiomyopathy: risk factors and predictors of outcome and change of mid-term ventricular function.

The partial left ventriculectomy (PLV) for end-stage dilated cardiomyopathy (DCM) which worked in some patients has been reported, although the hospital mortality is high. To reduce hospital mortality, we selected operative procedures of left ventricular (LV) restoration to improve the operative results. We analyzed the risk factors and predictors of outcome, and the mid-term changes of the LV function were determined. Between December 1996 and September 2000, 74 patients with non-ischemic DCM received LV restoration. The age ranged from 14 to 76 years (mean, 49.0+/-14.0 years), and there were 63 men and 11 women. The etiology of the DCM was idiopathic DCM in 49 patients, and dilated hypertrophic cardiomyopathy in seven patients and others in 18. The preoperative New York Heart Association (NYHA) functional class was 29 in class III and 45 in class IV, in which 32 patients depended on inotropic support. PLV or septal anterior ventricular exclusion (SAVE) was selected depending on the akinetic lesion of the LV based on the intraoperative echo-test. Fifty-six patients received elective operations, and emergency operations were performed in 18 patients. The risk factors and predictors of outcome were analyzed in 74 patients, and in 35 patients who survived more than 1 year after receiving LV restoration, the mid-term cardiac function was examined by cardiac echogram and catheterization. PLV was performed in 62 patients and SAVE in 12 patients. Concomitant mitral surgery was performed in 66 patients (89%) and tricuspid annuloplasty in 42 patients (57%). There were 15 hospital deaths and 13 patients died after discharge from the hospital (cardiac deaths in nine and non-cardiac deaths in four). In the 46 late survivors, the NYHA class was I or II in 42 patients and III in four patients. Selection of the procedure of LV restoration (P<0.01), elective operation (P<0.05), and the preoperative volume of LV (endodiastolic volume index of <180 ml/m(2); P<0.05) were risk factors and predictors influencing hospital and late death. After the operation, the LV function improved significantly and the improvement was maintained at the mid-term period; the LV ejection fraction was 31.8+/-7.9% (P<0.01) at 1 year from 23.0+/-7.3% preoperatively, left ventricular diastolic diameter was 62.8+/-10.9 (P<0.01) from 81.7+/-8.2 mm and the LV endosystolic volume index was 88.5+/-45.8 (P<0.05) from 162.6+/-41.6 ml/m(2). The operative results improved with the selection of the procedures, with elective operation, and mitral plasty for less cardiac dilatation. The mid-term results of clinical status and LV function showed the effectiveness of the operation.

Partial left ventriculectomy, ventriculoplasty or valvular surgery for idiopathic dilated cardiomyopathy - the role of intra-operative echocardiography.

The partial left ventriculectomy (PLV) is known to work in some patients with dilated cardiomyopathy (DCM), although this procedure does not work well in all patients and the operative mortality is higher than the other cardiac surgeries. In addition to PLV, left ventriculoplasty to exclude antero-septal wall or valvular surgery without left ventricle (LV) surgery can be also effective in patients with DCM. To improve the surgical results for dilated cardiomyopathy, we introduced echo-guided volume reduction test and evaluated the surgical procedures and the results on the surgery for DCM. Between December 1996 and July 1999, 56 patients with DCM (50 with idiopathic DCM, six with dilated hypertrophic cardiomyopathy) were surgically treated. Under the standard cardiopulmonary bypass, left ventricular motion was determined with color kinesis of echocardiogram and the lesion of akinetic wall was removed or excluded. After the initial PLV in 18 patients (initial group), operative procedures were selected in 21 with PLV, five with LV plasty, or 12 with valve surgery without LV surgery according to the findings of the LV wall motion by intraoperative echogram (select group). There were six hospital deaths and late follow-up deaths within 1 year in initial group, however, the mortality decreased significantly after the selection of the operative procedures; three hospital deaths and two late deaths in the select-group (P<0.05). Significant decrease of left ventricular diameter, the LV ejection fraction and endosystolic volume index were demonstrated after the LV surgery. The survival rate improved significantly after the selection of the operative procedures; 14 months survival rates was 50.0% in initial group and 73.1% in select group (P<0.05). Operative mortality decreased and late follow-up results improved after the selection of operative procedures according to the intraoperative volume reduction test.

Comparison of Clinical and Morphologic Cardiac Findings in Patients Having Cardiac Transplantation for Ischemic Cardiomyopathy, Idiopathic Dilated Cardiomyopathy, and Dilated Hypertrophic Cardiomyopathy

This article compares intergroup and intragroup clinical and morphologic findings in patients with ischemic cardiomyopathy (IC), idiopathic dilated cardiomyopathy (IDC), and dilated hypertrophic cardiomyopathy (HC) undergoing cardiac transplantation (CT). Few previous publications have described findings in native hearts explanted at the time of CT. The explanted heart in 92 patients having CT was examined in uniform manner with particular attention to the sizes of the ventricular cavities and the presence of and extent of ventricular scarring. Of the 92 hearts examined, 47 had IC, 35 had IDC, and 10 had dilated HC. Although considerable degrees of intragroup variation occurred, the mean degree of left ventricular dilatation was similar among the patients with IC, IDC, and dilated HC. All patients with IC had left ventricular free wall scarring more extensive than that involving the ventricular septum, but the intragroup variation in the amounts of scarring was considerable. Nine of the 10 patients with dilated HC also had ventricular wall scarring, but it was more extensive in the ventricular septum than in the left ventricular free wall and involvement of the right ventricular wall also was present. Eight (23%) of the 35 IDC patients also had grossly visible ventricular scars but they were small and only 1 of the 8 had coronary narrowing and that was not in the distribution of the scarring. Narrowing of 1 or more epicardial coronary arteries >75% in cross-sectional area by plaque was present in all 47 IC patients, in 8 of the 35 IDC patients (7 had no ventricular scars), and in none of the 10 dilated HC patients. Coronary angiography was the major clinical tool allowing separation of the IC, IDC, and HC patients. Coronary angiography did not detect narrowing in any of the 8 patients with IDC who were found to have coronary narrowing on anatomic study. Thus, among patients with IC, IDC, and dilated HC having CT, distinctive anatomic features allow separation of patients with IC, IDC, and dilated HC, but within each group considerable variation in left ventricular cavity size and extent of ventricular scarring occurs.

Cardioskeletal mitochondria1 myopathy associated with chronic magnesium deficiency

A 3-year-old boy presenting with convulsions and carpopedal spasm had hypomagnesemia and hypermagnesuria due to congenital magnesium-losing nephropathy. Despite chronic oral and intermittent intravenous magnesium supplementation, he remained chronically hypomagnesemic. At age 4, he developed a progressive proximal myopathy and dilated hypertrophic cardiomyopathy that ultimately contributed to his death at age 14 years. Skeletal and cardiac muscle specimens showed a mitochondrial myopathy with increased numbers of enlarged, structurally abnormal mitochondria. Muscle magnesium content was markedly decreased. Chronic oral and intermittent intravenous magnesium supplementation may be inadequate to prevent the progressive cardioskeletal myopathy associated with the chronic magnesium deficiency of congenital magnesium-losing nephropathy.