Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families.

We studied mutations of the adult voltage-gated skeletal muscle sodium channel gene in 12 families, from diverse ethnic backgrounds, with hyperkalemic periodic paralysis (HyperPP). We describe a novel procedure, using ligase chain reaction (LCR), to simultaneously identify two different point mutations (previously described) and one rare, apparently benign polymorphism that results in a nonconservative amino acid substitution. Three of 12 families showed the Met1592Val mutation, and six of 12 had the Thr704Met mutation. The mutation in three of the 12 families was not identified. In one of these three families, the disease was not linked to the adult voltage-gated sodium channel gene, suggesting the existence of a clinically similar but genetically distinct form of HyperPP. Genotype/phenotype correlations based on patient records and interviews in these families showed the variable and subjective nature of the illness, although the clinical distinctions between hyperkalemic periodic paralysis and paramyotonia congenita were reinforced by the molecular data.

Restriction fragment length polymorphism of the T cell receptor beta-chain gene in Chinese patients with thyrotoxic hypokaleamic periodic paralysis and Graves' disease.

Restriction fragment length polymorphism (RFLP) of the T cell receptor beta-chain gene was studied in two groups of Chinese thyrotoxic patients, those with thyrotoxic hypokaleamic periodic paralysis (THPP) and those with Graves' Disease (GD). DNA digested with restriction enzymes Bgl II, Bam HI, Eco RI, Pvu II and Taq I were hybridized to a 770 bp TcR beta cDNA probe containing the joining (J) and constant (C) region segments. The TcR beta/Bgl II polymorphism of 9.2 kb and 10 kb fragments were observed in THPP, GD and normal controls. The genotype frequencies of this polymorphism, however, did not differ between patients (THPP or GD) and controls. These results, therefore, do not support the presence of an association between the TCR beta/Bgl II RFLP and THPP nor with GD susceptibility. Finally, restriction analysis of DNA from our patients and normal controls using enzymes Bam HI, Eco RI, Pvu II and Taq I with the T cell receptor beta-chain gene did not show polymorphisms, and were therefore not informative.

Thyrotoxic hypokalemic periodic paralysis: report of four cases in black American males.

Thyrotoxic periodic paralysis (TPP) is an unusual complication of a fairly common disease affecting mostly Asian males. In the United States, there have been several reports of TPP in different ethnic populations and it appears that the incidence is approximately one-tenth of that found in Asian countries. Only six reports of TPP in African-Americans could be found in the literature; however, we are reporting four cases diagnosed within a 13-year period at our institution. We conclude that TPP may occur more often in Blacks than previously suspected and should be considered when patients present with unexplained hypokalemia, muscular weakness and rhabdomyolysis. The epidemiology, clinical manifestations, pathophysiology, and treatment of TPP are reviewed.

Thyrotoxic periodic paralysis: a case report and review of the literature.

Hypokalemic periodic paralysis occurring in thyrotoxicosis is rare in Caucasians and is not often highlighted as an endocrine emergency. Periodic paralysis, without familial background, manifests only in the thyrotoxic patient. Thyrotoxic periodic paralysis is a self-limiting disorder that is cured by the treatment of the underlying hyperthyroidism. We report an unusual case of acute onset weakness from thyrotoxic periodic paralysis in a young Chinese migrant who had a normal serum potassium level at the time of initial presentation, though on subsequent presentation one week later, he had the typically associated hypokalemia. We also review the literature on thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis in a Jamaican male.

Thyrotoxic periodic paralysis is a rare endocrine disorder most prevalent among individuals of Asian descent that presents as proximal muscle weakness, hypokalemia, and signs of hyperthyroidism. We present the case report of a patient with previously undiagnosed hyperthyroidism, protracted muscle weakness with transient exacerbations, and nocturnal onset of periodic paralysis affecting the upper and lower limbs.

[Periodic paramyotonic paralysis]. / Periodicheskii paramiotonicheskii paralich.

A rare case of Eulenburg's paramyotonia and periodic paralysis combination is described in one family. The question of whether the disease presents a nosological entity is discussed with due consideration of its clinical polymorphism and the data of literature. Mapping the genes determining the disease would be decisive in this respect.

Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3.

Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.

Thyrotoxic periodic paralysis: reports of seven patients presenting with weakness in an Asian emergency department.

OBJECTIVES: This study was done to describe the features of thyrotoxic periodic paralysis in young Asian men. METHODS: Seven male patients were enlisted who presented to the emergency department over a period of three years with weakness and paralysis in the morning. RESULTS: Initial electrolyte studies revealed hypokalaemia in these patients, and later thyroid function tests confirmed thyrotoxicosis for all. Only two of these patients had clinical symptoms and signs of thyrotoxicosis, the others being asymptomatic. CONCLUSIONS: Early morning paralysis can be the first manifestation of hyperthyroidism in Asian men, without the other more typical symptoms of weight loss, increased appetite, excitability, sweaty palms or goitre. Treatment to a euthyroid state will ameliorate the syndrome.

Thyrotoxic periodic paralysis in a Maori patient.

A case of thyrotoxic periodic paralysis (TPP) in a patient of Maori heritage is described. The epidemiology, aetiology and pathogenesis of TPP are discussed. The case demonstrates that neurological examination and biochemical findings may be normal between episodes of paralysis. Given that there is much racial variation in the prevalence of TPP, and the suggestion that non-thyrotoxic periodic paralysis may be more prevalent in Maori, the case highlights the need for more research into the prevalence and pathogenesis of TPP in Maori patients.

Thyrotoxic periodic paralysis in a Jamaican male

Thyrotoxic periodic paralysis is a rare endocrine disorder most prevalent among individuals of Asian descent that presents as proximal muscle weakness, hypokalemia, and signs of hyperthyroidism. We present the case report of a patient with previously undiagnosed hyperthyroidism, protracted muscle weakness with transient exacerbations, and nocturnal onset of periodic paralysis affecting the upper and lower limbs (AU)