Recurrent Muscle Weakness Research Articles

A novel CACNA1S gene variant in a child with hypokalemic periodic paralysis: a case report and literature review

BackgroundThe CACNA1S gene encodes the alpha 1 S-subunit of the voltage-gated calcium channel, which is primarily expressed in the skeletal muscle cells. Pathogenic variants of CACNA1S can cause hypokalemic periodic paralysis (HypoPP), malignant hyperthermia susceptibility, and congenital myopathy. We aimed to study the clinical and molecular features of a male child with a CACNA1S variant and depict the molecular sub-regional characteristics of different phenotypes associated with CACNA1S variants.Case presentationWe presented a case of HypoPP with recurrent muscle weakness and hypokalemia. Genetic analyses of the family members revealed that the proband had a novel c.497 C > A (p.Ala166Asp) variant of CACNA1S, which was inherited from his father. The diagnosis of HypoPP was established in the proband as he met the consensus diagnostic criteria. The patient and his parents were informed to avoid the classical triggers of HypoPP. The attacks of the patient are prevented by lifestyle changes and nutritional counseling. We also showed the molecular sub-regional location of the variants of CACNA1S which was associated with different phenotypes.ConclusionsOur results identified a new variant of CACNA1S and expanded the spectrum of variants associated with HypoPP. Early genetic diagnosis can help avoid diagnostic delays, perform genetic counseling, provide proper treatment, and reduce morbidity and mortality.

TANGO2 Deficiency Disorder: Two Cases of Developmental Delay Preceding Metabolic Crisis

BackgroundTANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene. MethodsWe report the clinical phenotype of two children with TANGO2 deficiency disorder. ResultsPatient 1 is a female child presenting with developmental delay and microcephaly during the second year of life, who evolved with severe cognitive impairment, facial dysmorphisms, spastic paraparesis, and atonic seizures. At age 13 years, she was hospitalized due to an episode of rhabdomyolysis complicated with cardiac arrhythmia and hypothyroidism. Patient 2 is a female child with dysmorphic facial features, cleft palate, and developmental delay who was diagnosed with DiGeorge syndrome. At age three years, she presented with an acute episode of severe rhabdomyolysis in the context of human herpesvirus 6 infection. After the resolution of this acute episode, she maintained recurrent muscle weakness with axial hypotonia and progressive spasticity of the lower extremities. In both patients, diagnosis of TANGO2 deficiency disorder was only confirmed after an acute metabolic crisis. ConclusionsA high index of suspicion for TANGO2 deficiency disorder is needed in patients with developmental delay or other neurological symptoms and episodic rhabdomyolysis.

A novel mutation in TANGO2 gene associated with recurrent muscle weakness with rhabdomyolysis , metabolic encephalopathy and cardiac arrhythmia: a case report

Background TANGO2 depletion was found to cause clinically recognizable multi-organ involvement disorder in pediatrics with episodic muscle weakness recurrent rhabdomyolysis, intellectual disability, metabolic encephalomyopathic crises and cardiac arrhythmia. TANGO2 deficiency is also referred to as \"metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration\" (MECRCN) in OMIM. * 616830 Case presentation We report a case of a 4-year-old Saudi boy from a consanguineous Saudi family with two uncles deceased at 3 year of age with recurrent muscle weakness and hyperammonemia of unknown cause .Patient in last attack progressed to severe metabolic encephalomyopathic crisis that required assisted ventilation for 4 months, complicated with life threatening cardiac tachyarrhythmia. Laboratory findings of hypoglycemia, mild hyperammonemia , severely elevated plasma Creatine Kinase, myoglobinuria , lactic acidosis and increased TSH concentration indicating hypothyroidism have been documented. The clinical profile was highly suggestive of TANGO2-realted disorder. Direct DNA sequence analysis of the entire coding regions of TANGO2 gene identified a novel homozygous deletion for three nucleotides in exon 2 (c.11_13delTCT) resulting in amino acid deletion (phenylalanine) at position 5. Conclusion This report illustrates the importance of collating clinical data and keeping a high index of suspicion in order to reach to the diagnosis.

Thiamine-responsive pyruvate dehydrogenase complex deficiency presenting as recurrent muscle weakness: Identification of a novel mutation (p.T111I) in the PDHA1 gene.

Thiamine-responsive pyruvate dehydrogenase complex deficiency presenting as recurrent muscle weakness: Identification of a novel mutation (p.T111I) in the PDHA1 gene.

The first case of chronic inflammatory demyelinating polyneuropathy after transsexualism and continuous testosterone administration

AbstractWe report on a 35‐year‐old man who had gender dysphoria following unilateral ovariectomy and then received continuous testosterone injection for nine years, inducing chronic inflammatory demyelinating polyneuropathy (CIDP). He developed recurrent muscle weakness and numbness in the extremities and displayed demyelinating neuropathy, detected by nerve conduction studies and a sural nerve biopsy. Repeated intravenous immunoglobulin (IVIg) therapy and the administration of oral prednisolone improved symptoms and inhibited their recurrence. A relatively high level of serum testosterone as a genetic female might have caused the neurotoxicity of the peripheral nerve, leading to CIDP.

Hypokalemic Periodic Paralysis: Reports of Two Cases and Brief Review

Hypokalemic periodic paralysis (HPP) is a rare autosomal dominant channelopathy characterized by skeletal muscle weakness or paralysis when there is a fall in potassium levels in blood. Weakness may be mild and limited to certain muscle groups or more severe causing generalized paralysis. During an attack, reflexes may be diminished or absent. Attacks may last for a few hours or persist for several days, ultimately resulting in complete recovery. Some patients may develop chronic muscle weakness later in life. Recurrent muscle weakness accompanied by hypokalemia and exclusion of other causes help establish the diagnosis. Potassium supplementation is the mainstay of treatment of acute illness. Lifestyle modification with or without pharmacotherapy in the form of carbonic anhydrase inhibitors and/ or spironolactone can prevent future attacks. Here, we present two cases of HPP, the first one had no positive family history and responded to oral potassium and spironolactone, while the second case had family history suggestive of HPP and was managed with potassium and eplerenone.
 Birdem Med J 2019; 9(1): 74-79

Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations

The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ∼34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations.

A Case of Nonfatal Ventricular Arrhythmia Due to Thyrotoxic Periodic Paralysis in a Saudi Patient as an Initial Presentation of Graves’ Disease

Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism characterized by recurrent muscle weakness and hypokalemia. It has been commonly reported in non-Asian populations. Four cases were reported in Saudis so far, and one had a life-threatening arrhythmia. We describe an additional case of a 28-year-old apparently healthy Saudi male patient, who presented with acute paraparesis associated with hypokalemia (K: 2.0 mmol/L), complicated by ventricular tachycardia and cardiac arrest. He was successfully resuscitated and his hypokalemia was corrected. A diagnosis of Graves’ disease associated with TPP was made. He was initially treated with carbimazole and β-blockers and then given a definitive therapy with radioactive iodine, which showed a good response. This case highlights the importance of early recognition and prompt treatment of TPP as a differential diagnosis for muscle weakness. A brief review of TPP and associated arrhythmia is included.

Safe use of rocuronium for a post-polio syndrome patient

To the Editor: Patients with ‘‘post-polio syndrome’’ can experience recurrent muscle weakness years after acute poliovirus infection [1]. We report a case of a 64-year-old woman who was scheduled for mastectomy. We report the effect of rocuronium, as evaluated by train-of-four (TOF) monitoring of this patient. She had undergone two caesarean sections, under spinal anesthesia with prolongation of hypesthesia and under general anesthesia with delayed awakening, which was speculated to be caused by residual neuromuscular blockade (NMB). She presented with muscle weakness in the lower extremities and the right upper extremity (manual muscle testing 3/5), but spirometry values were normal. After induction of general anesthesia, neuromuscular monitoring was started by use of TOF monitoring of the right adductor pollicis muscle. The TOF ratio was 100 %. Rocuronium (0.6 mg/kg) was used for NMB. Anesthesia was maintained with sevoflurane and remifentanil. The change of TOF ratio is shown in the figure. Because TOF monitoring showed the ratio was 100 % at the end of surgery, NMB was not reversed. She did not report any respiratory complaints. Patients with post-polio syndrome are known to be potentially hypersensitive to NMBs, anesthetic agents, and opioids [1]. Because they have fewer motor neurons than normal [1], shorter acting non-depolarizing NMBs are desirable and neuromuscular monitoring is necessary. In our case, it seems likely she did not experience prolongation of the rocuronium effect. Moreover, we did not observe any signs of hypersensitivity to sevoflurane or remifentanil. Prolongation of the effects of these drugs is likely to depend on the extent of paralysis. Recurarization after spontaneous complete recovery does not occur with non-depolarizing NMBs. Although we did not reverse the rocuronium, it might be better to administer sugammadex. Conflict of interest None.

Surgical treatment for thyrotoxic hypokalemic periodic paralysis: case report

Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare, potentially life-threatening endocrine emergency. It is characterized by recurrent muscle weakness and hypokalemia. Because many THPP patients do not have obvious symptoms and signs of hyperthyroidism, misdiagnosis may occur. The published studies revealed that definitive therapy for THPP is control of hyperthyroidism by medical therapy, radioactive iodine or surgery, but the long-term post-operative follow-up result was not observed. We reported two cases of medically refractory THPP with recurrent paralysis of extremities and hypokalemia, and both were combined with thyroid nodules. Both patients were treated with total thyroidectomy; the pathology revealed that one is Graves' disease with thyroid papillary carcinoma, and the other is adenomatous goiter with papillary hyperplasia. No episode of periodic paralysis was noted and laboratory evaluation revealed normal potassium level during the post-operative follow up. Our experience suggests that total thyroidectomy by experienced surgeon is an appropriate and definite treatment for medically refractory THPP, especially in cases combined with thyroid nodules.

Treatment of Adult Inflammatory Myositis With Rituximab

Rituximab is a genetically engineered chimeric, murine/human monoclonal antibody directed against the CD20 antigen on B-cells. Recent studies of inflammatory myopathy have shown that B-cells are important in the etiopathogenesis of these diseases, and therefore suggest a role for B-cell depletion therapy in idiopathic inflammatory myopathy. The few case reports and small series that have been published suggest that anti-B-cell therapy is effective for the clinical manifestations of inflammatory myopathy. To report our experience using rituximab to treat 3 patients with refractory idiopathic inflammatory myopathy (IIM), and to review and discuss the available literature regarding reported experience using rituximab in treating IIM. We describe the clinical courses of 3 patients with IIM treated by us with rituximab after unsatisfactory responses to conventional therapy. We performed a search of the English language literature utilizing PubMed, and identified 8 articles that also described the use of rituximab for treatment of IIM. Improvement in our patients was manifested by an increase in muscle strength and decline in creatinine kinase levels in all 3 patients. Recurrent muscle weakness and elevated muscle enzymes occurred in 2 patients postinfusion; retreatment with rituximab resulted in similar clinical improvement. Our experience, and that 20 of 21 patients described in 8 cited reports demonstrate a favorable clinical response in patients treated with B-cell depletion therapy for IIM. Early uncontrolled clinical experience indicates that rituximab may be a valuable therapeutic agent for treatment of refractory IIM. Further investigation regarding the optimal dosing regimen, treatment length, and long-term safety profile of rituximab therapy for IIM is warranted.