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Familial periodic paralysis

Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis (rarely death) from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move (a channelopathy). more...

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It should be noted that the symptoms of periodic paralysis can also be caused by hyperthyroidism; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.

Types

Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent need carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:

Hypokalemic periodic paralysis (OMIM 170400), where potassium leaks into the muscle cells from the bloodstream.

Hyperkalemic periodic paralysis (OMIM 170500), where potassium leaks out of the cells into the bloodstream.

Paramyotonia congenita (OMIM 168300), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down.

Andersen-Tawil syndrome (OMIM 170390), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosis (curvature of the spine), webbing between the second and third toes or fingers (clinodactyly), crooked fingers, a small jaw (micrognathia) and low-set ears.

Diagnosis

This disease is unusually difficult to diagnose. Patients often report years of wrong diagnosis and treatments that made them worse instead of better. Part of this may be that migraines are present in up to 50% of patients and can cause a confusing array of symptoms including headaches, speech difficulties and visual, auditory or sensory auras. DNA testing is available for only a half dozen common gene mutations, while dozens of known mutations are possible but are not routinely tested. EMG results will be normal except during attacks. A properly performed Exercise EMG (Compound Muscle Amplitude Potential Test) can provide an accurate diagnosis in better than 80% of cases. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used.

Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis. These diseases are not the same as having a very low level of potassium (hypokalemia) or high potassium (hyperkalemia) and must not be treated as such. The total body store of potassium is usually normal; it is just in the wrong place.

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Residue-specific effects on slow inactivation at V787 in D2-S6 of Na(v)1.4 sodium channels
From Biophysical Journal, 10/1/01 by O'Reilly, John P

ABSTRACT Slow inactivation in voltage-gated sodium channels (NaChs) occurs in response to depolarizations of seconds to minutes and is thought to play an important role in regulating membrane excitability and action potential firing patterns. However, the molecular mechanisms of slow inactivation are not well understood. To test the hypothesis that transmembrane segment 6 of domain 2 (D2-S6) plays a role in NaCh slow inactivation, we substituted different amino acids at position V787 (valine) in D2-S6 of rat skeletal muscle NaCh mu1 (Na^sub v^1.4). Whole-cell recordings from transiently expressed NaChs in HEK cells were used to study and compare slow inactivation phenotypes between mutants and wild type. V787K (lysine substitution) showed a marked enhancement of slow inactivation. V787K enters the slow-inactivated state ==100x faster than wild type (tau^sub 1^ == 30 ms vs. ==3 s), and occurs at much more hyperpolarized potentials than wild type (V^sub 1/2^ of s^sub inf^ curve == -- 130 mV vs.== -75 mV). V787C (cysteine substitution) showed a resistance to slow inactivation, i.e., opposite to that of V787K. Entry into the slow inactivation state in V787C was slower (tau^sub 1^ == 5 s), less complete, and less voltage-dependent (V^sub 1/2 of s^sub inf^ curve == -50 mV) than in wild type. Application of the cysteine modification agent methanethiosulfonate ethylammonium (MTSEA) to V787C demonstrated that the 787 position undergoes a relative change in molecular conformation that is associated with the slow inactivation state. Our results suggest that the V787 position in Na^sub v^1.4 plays an important role in slow inactivation gating and that molecular rearrangement occurs at or near residue V787 in D2-S6 during NaCh slow inactivation.

REFERENCES

Akabas, M. H., D. A. Stauffer, M. Xu, and A. Karlin. 1992. Acetylcholine receptor channel structure probed in cysteine-substitution mutants. Science. 258:307-310.

Aldrich, R. W., D. P. Corey, and C. F. Stevens. 1983. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature. 306:436-441.

Armstrong, C. M., F. Bezanilla, and E. Rojas. 1973. Destruction of sodium conductance inactivation in squid axons perfused with pronase. J. Gen. Physiol. 62:375-391.

Bendahhou, S., T. R. Cummins, A. F. Hahn, S. Langlois, S. G. Waxman, and L. J. Ptacek. 2000. A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. J. Clin. Invest. 106:431-438.

Cannon, S. C., and S. M. Strittmatter. 1993. Functional expression of sodium channel mutations identified in families with periodic paralysis. Neuron. 10:317-326.

Cota, G., and C. M. Armstrong. 1989. Sodium channel gating in clonal pituitary cells. The inactivation step is not voltage dependent. J. Gen. Physiol, 94:213-232.

Cummins, T. R., S. D. Dib-Hajj, J. A. Black, A. N. Akopian, J. N. Wood, and S. G. Waxman. 1999. A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J. Neurosci. 19:RC43.

Cummins, T. R., and F. J. Sigworth. 1996. Impaired slow inactivation in mutant sodium channels. Biophys. J. 71:227-236.

Featherstone, D. E., J. E. Richmond, and P. C. Ruben. 1996. Interaction between fast and slow inactivation in Skm sodium channels. Biophys. J. 71:3098-3109.

Gellens, M. E., A. L. J. George, L.-Q. Chen, M. Chahine, R. Horn, R. L. Barchi, and R. G. Kallen. 1992. Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltagedependent sodium channel. Proc. Natl. Acad. Sci. U.S.A. 89:554-558.

Graham, F. L., and A. J. Eb. 1973. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 52:456-467. Hamill, 0. P., A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth. 1981.

Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 391:85-100.

Hayward, L. J., R. H. J. Brown, and S. C. Cannon. 1997. Slow inactivation differs among mutant Na channels associated with myotonia and periodic paralysis. Biophys. J. 72:1204-1219.

Hayward, L. J., G. M. Sandoval, and S. C. Cannon. 1999. Defective slow inactivation of sodium channels contributes to familial periodic paralysis. Neurology. 52:1447-1453.

Heinemann, S. H., H. Terlau, W. Stuhmer, K. Imoto, and S. Numa. 1992. Calcium channel characteristics conferred on the sodium channel by single mutations. Nature. 356:441-443.

Hille, B. 1989. The Sharpey-Schafer lecture. Ionic channels: evolutionary origins and modern roles. Q. J. Exp. Physiol. 74:785-804.

Hille, B. 1992. Ionic Channels of Excitable Membranes. Sinauer Associates, Sunderland, MA.

Hodgkin, A. L., and A. E. Huxley. 1952:A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. (Land.). 117:500-544.

Holmgren, M., Y. Liu, Y. Xu, and G. Yellen. 1996. On the use of thiol-modifying agents to determine channel topology. Neuropharmacology. 35:797-804.

Holmgren, M., K. S. Shin, and G. Yellen. 1998. The activation gate of a voltage-gated K+ channel can be trapped in the open state by an intersubunit metal bridge. Neuron. 21:617-621.

Khodorov, B. 1. 1985. Batrachotoxin as a tool to study voltage-sensitive sodium channels of excitable membranes. Prog. Biophys. Mol. Biol. 45:57-148.

Lipkind, G. M., and H. A. Fozzard. 2000. KcsA crystal structure as framework for a molecular model of the Na(+) channel pore. Biochemistry. 39:8161-8170.

McPhee, J. C., D. S. Ragsdale, T. Scheuer, and W. A. Catterall. 1998. A critical role for the S4-SS intracellular loop in domain IV of the sodium channel a-subunit in fast inactivation. J. Biol. Chem. 273:1121-1129.

Noda, M., T. Ikeda, T. Kayano, H. Suzuki, H. Takeshima, M. Kurasaki, H. Takahashi, and S. Numa. 1986. Existence of distinct sodium channel messenger RNAs in rat brain. Nature. 320:188-192.

Noda, M., S. Shimizu, T. Tanabe, T. Takai, T. Kayano, T. Ikeda, H. Takahashi, H. Nakayama, Y. Kanaoka, and N. Minamino. 1984. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature. 312:121-127.

O'Leary, M. E. 1998. Characterization of the isoform-specific differences in the gating of neuronal and muscle sodium channels. Can. J. Physiol. Pharmacol. 76:1041-1050.

O'Reilly, J. P., S.-Y. Wang, R. G. Kallen, and G. K. Wang. 1999. Comparison of slow inactivation in human heart and rat skeletal muscle Na channel chimeras. J. Physiol. (Lond.). 515.1:61-73.

O'Reilly, J. P., S.-Y. Wang, and G. K. Wang. 2000. A point mutation in domain 4-segment 6 of the skeletal muscle sodium channel produces an atypical inactivation state. Biophys. J. 78:773-784.

Patton, D. E., J. W. West, W. A. Catterall, and A. L. Goldin. 1992. Amino acid residues required for fast Na+-channel inactivation: charge neutralizations and deletions in the III-IV linker. Proc. Natl. Acad. Sci. U.S.A. 89:10905-10909.

Rudy, B. 1978. Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance. J. Physiol. (Lond.). 283:1-21.

Ruff, R. L., L. Simoncini, and W. Stuhmer. 1988. Slow sodium channel inactivation in mammalian muscle: a possible role in regulating excitability. Muscle Nerve. 11:502-510.

Sawczuk, A., R. K. Powers, and M. D. Binder. 1995. Spike frequency adaptation studied in hypoglossal motoneurons of the rat. J. Neurophysiol. 73:1799-1810.

Smith, M. R., and A. L. Goldin. 1997. Interaction between the sodium channel inactivation linker and domain III S4-S5. Biophys. J. 73: 1885-1895.

Struyk, A. F., K. A. Scoggan, D. E. Bulman, and S. C. Cannon. 2000. The human skeletal muscle Na channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation. J. Neurosci. 20:8610-8617.

Stuhmer, W., F. Conti, H. Suzuki, X. D. Wang, M. Noda, N. Yahagi, H. Kubo, and S. Numa. 1989. Structural parts involved in activation and inactivation of the sodium channel. Nature. 339:597-603.

Takahashi, M. P., and S. C. Cannon. 1999. Enhanced slow inactivation by V445M: a sodium channel mutation associated with myotonia. Biophys. J. 76:861-868.

Trimmer, J. S., S. S. Cooperman, S. A. Tomiko, J. Y. Zhou, S. M. Crean, M. B. Boyle, R. G. Kallen, Z. H. Sheng, R. L. Barchi, and F. J. Sigworth. 1989. Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron. 3:33-49.

Tytgat, J., and P. Hess. 1992. Evidence for cooperative interactions in potassium channel gating. Nature. 359:420-423.

Ukomadu, C., J. Zhou, F. J. Sigworth, and W. S. Agnew. 1992. Il Na+ channels expressed transiently in human embryonic kidney cells: biochemical and biophysical properties. Neuron. 8:663-676.

Vedantham, V., and S. C. Cannon. 2000. Rapid and slow voltagedependent conformational changes in segment IVS6 of voltage-gated Na(+) channels. Biophys. J. 78:2943-2958.

Vilin, Y. Y., N. Makita, A. L. J. George, and P. C. Ruben. 1999. Structural determinants of slow inactivation in human cardiac and skeletal muscle sodium channels. Biophys. J. 77:1384-1393.

Wang, S.-Y., M. Barile, and G. K. Wang. 2001. Disparate role of Na(+) channel D2-S6 residues in batrachotoxin and local anesthetic action. Mol. Pharmacol. 59:1100-1107.

Wang, S.-Y., C. Nau, and G. K. Wang. 2000. Residues in Na(+) channel D3-S6 segment modulate both batrachotoxin and local anesthetic affinities. Biophys. J. 79:1379-1387.

Wang, S.-Y., and G. K. Wang. 1997. A mutation in segment I-S6 alters slow inactivation of sodium channels. Biophys. J. 72:1633-1640. Wang, S.-Y., and G. K. Wang. 1998. Point mutations in segment I-S6

render voltage-gated Na+ channels resistant to batrachotoxin. Proc. Natl. Acad. Sci. U.S.A. 95:2653-2658.

Wang, S.-Y., and G. K. Wang. 1999. Batrachotoxin-resistant Na+ channels derived from point mutations in transmembrane segment D4-S6. Biophys. J. 76:3141-3149.

Wang, D. W., K. Yazawa, A. L. J. George, and P. B. Bennett. 1996. Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. Proc. Natl. Acad. Sci. U.S.A. 93: 13200-13205.

Yang, N., A. L. George, and R. Horn. 1997. Probing the outer vestibule of a sodium channel voltage sensor. Biophys. J. 73:2260-2268. Yarov-Yarovoy, V., J. Brown, E. M. Sharp, J. J. Clare, T. Scheuer, and

W. A. Catterall. 2001. Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na+ channel alpha subunit. J. Biol. Chem. 276:20-27.

Yellen, G. 1998. The moving parts of voltage-gated ion channels. Q. Rev. Biophys. 31:239-295.

John P. O'Reilly,* Sho-Ya Wang,^ and Ging Kuo Wang*

*Department of Anesthesia Research, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ^Department of Biological Sciences, State University of New York at Albany, Albany, New York 12222 USA

Received for publication 1 June 2001 and in final form 12 July 2001.

Address reprint requests to John P. O'Reilly, Ph.D., Department of Anesthesia Research, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. Tel.: 617-732-6883; Fax: 617-730-2801; E-mail: joreilly@zeus.bwh.harvard.edu.

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