Acute hypocalcemia and metabolic alkalosis in children on cation-exchange resin therapy

Background. Sodium polystyrene sulfonate (SPS) is a chelating agent used for the treatment of hyperkalemia. SPS has a wide range of exchange capacity requiring close monitoring of serum electrolytes. We observed two patients who developed acute hypocalcemia and increased metabolic alkalosis after initiating SPS therapy. We report these cases to draw attention to the potential risk of this medication in pediatric patients. Case Diagnosis/Treatment. Two children with chronic kidney disease on dialysis were started on SPS for hyperkalemia. Within a week after initiation of the medication, both patients developed hypocalcemia on routine labs without overt clinical manifestations. The hypocalcemia was rapidly corrected with oral supplementation and discontinuation of SPS. Conclusions. Severe hypocalcemia can develop after SPS therapy. The metabolic alkalosis in these patients associated with the hypocalcemia put them at increased risk for complications. Hence, careful attention must be paid to the state of calcium metabolism in all patients receiving SPS. Often calcium supplementation is required to maintain normal calcium levels

Case report: Malignant hypertension associated with catecholamine excess in a patient with Leigh syndrome

BACKGROUND: Leigh syndrome is a progressive neurodegenerative mitochondrial disorder caused by multiple genetic etiologies with multisystemic involvement that mostly affecting the central nervous system with high rate of premature mortality. CASE PRESENTATION: We present a 3-year, 10 month-old female patient with Leigh syndrome complicated by renal tubular acidosis, hypertension, gross motor delay, who presented with hypertensive emergency, persistent tachycardia, insomnia and irritability. Her previous genetic workup revealed a pathogenic variant in the MT-ND5 gene designated as m.13513G \u3e A;p.Asp393Asn with a heteroplasmy of 69%. She presented acutely with malignant hypertension requiring intensive care unit admission. Her acute evaluation revealed elevated serum and urine catecholamines, without an identifiable catecholamine-secreting tumor. After extensive evaluation for secondary causes, she was ultimately found to have progression of her disease with new infarctions in her medulla, pons, and basal ganglia as the most likely etiology of her hypertension. She was discharged home with clonidine, amlodipine and atenolol for hypertension management. This report highlights the need to recognize possible autonomic dysfunction in mitochondrial disease and illustrates the challenges for accurate and prompt diagnosis and subsequent management of the associated manifestations. This association between catecholamine induced autonomic dysfunction and Leigh syndrome has been previously reported only once with MT-ND5 mutation. CONCLUSIONS: Elevated catecholamines with malignant secondary hypertension may be unique to this specific mutation or may be a previously unrecognized feature of Leigh syndrome and other mitochondrial complex I deficient syndromes. As such, patients with Leigh syndrome who present with malignant hypertension should be treated without the need for extensive work-up for catecholamine-secreting tumors

A case of congenital nephrotic syndrome with crescents caused by a novel compound heterozygous pairing of NPHS1 genetic variants

Congenital nephrotic syndrome is an autosomal recessive inherited disorder that manifests as steroid-resistant massive proteinuria in the first three months of life. Defects in the glomerular filtration mechanism are the primary etiology. We present a child who developed severe nephrotic syndrome at two weeks of age and eventually required a bilateral nephrectomy. Genetic testing revealed compound heterozygous variants i

Systemic Myostatin Inhibition via Liver-Targeted Gene Transfer in Normal and Dystrophic Mice

Background: Myostatin inhibition is a promising therapeutic strategy to maintain muscle mass in a variety of disorders, including the muscular dystrophies, cachexia, and sarcopenia. Previously described approaches to blocking myostatin signaling include injection delivery of inhibitory propeptide domain or neutralizing antibodies. Methodology/Principal Findings: Here we describe a unique method of myostatin inhibition utilizing recombinant adenoassociated virus to overexpress a secretable dominant negative myostatin exclusively in the liver of mice. Systemic myostatin inhibition led to increased skeletal muscle mass and strength in control C57 Bl/6 mice and in the dystrophindeficient mdx model of Duchenne muscular dystrophy. The mdx soleus, a mouse muscle more representative of human fiber type composition, demonstrated the most profound improvement in force production and a shift toward faster myosin-heavy chain isoforms. Unexpectedly, the 11-month-old mdx diaphragm was not rescued by long-term myostatin inhibition. Further, mdx mice treated for 11 months exhibited cardiac hypertrophy and impaired function in an inhibitor dose–dependent manner. Conclusions/Significance: Liver-targeted gene transfer of a myostatin inhibitor is a valuable tool for preclinical investigation of myostatin blockade and provides novel insights into the long-term effects and shortcomings of myostatin inhibition o

Relations between plasma microRNAs, echocardiographic markers of atrial remodeling, and atrial fibrillation: Data from the Framingham Offspring study

BACKGROUND: Circulating microRNAs may reflect or influence pathological cardiac remodeling and contribute to atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to identify candidate plasma microRNAs that are associated with echocardiographic phenotypes of atrial remodeling, and incident and prevalent AF in a community-based cohort. METHODS: We analyzed left atrial function index (LAFI) of 1788 Framingham Offspring 8 participants. We quantified expression of 339 plasma microRNAs. We examined associations between microRNA levels with LAFI and prevalent and incident AF. We constructed pathway analysis of microRNAs\u27 predicted gene targets to identify molecular processes involved in adverse atrial remodeling in AF. RESULTS: The mean age of the participants was 66 +/- 9 years, and 54% were women. Five percent of participants had prevalent AF at the initial examination and 9% (n = 157) developed AF over a median 8.6 years of follow-up (IQR 8.1-9.2 years). Plasma microRNAs were associated with LAFI (N = 73, p \u3c 0.0001). Six of these plasma microRNAs were significantly associated with incident AF, including 4 also associated with prevalent AF (microRNAs 106b, 26a-5p, 484, 20a-5p). These microRNAs are predicted to regulate genes involved in cardiac hypertrophy, inflammation, and myocardial fibrosis. CONCLUSIONS: Circulating microRNAs 106b, 26a-5p, 484, 20a-5p are associated with atrial remodeling and AF