Hereditary angioneurotic edema and Charcot*Marie..Tooth disease in the same family PETER G. FERNANDEZ,*t MD, MRCP (GLASG), MRCP (UK), FRCP[C]; JAMES H. DAY,t MD, FRCP[C]; NANCY E. SIMPSON4 PH D. PRINCE K. ZACHARIAH,* PH D
In one family two genetic diseases were transmitted as autosomal dominant traits; hereditary angioneurotic edema was inherited from the paternal side and Charcot-Marie-Tooth disease from the maternal side of the family. The conditions occurred separately in 8 and 11 members respectively and together (an exceedingly rare occurrence) in 3. Of six siblings, two girls and four boys, all had Charcot-Marie-Tooth disease, and three, the two girls and one of the boys, also had hereditary angioneurotic edema.
un oedeme angioneurotique hereditaire a ete transmis du c6te paternel et une amyotrophie peroniere de CharcotMarie-Tooth est venue du c6t6 matemel de Ia famille. Ces conditions sont survenues separement chez respective. ment 8 et 11 membres de Ia famille, et ensemble (un fait excessivement rare) chez 3. D'une fratrie de six, deux filles et quatre gar;ons, tous souffraient d'amyotrophie peroniere de Charcot-Marie-Tooth et trois, les deux filles et un des gar.ons, avaient aussi un oedeme angioneurotique.
Dans une famille deux maladies genetiques ont ete transmises comme des traits autosomiques dominants;
Osler1 in 1888 was the first to describe hereditary angioneurotic edema, a condition characterized by localized swelling of the skin on From *the faculty of medicine, Memorial various parts of the body, abdominal University of Newfoundland, St. John's, pain and laryngeal obstruction due and tthe department of medicine and Uhe division of genetics, department of pediatrics, Queen's University, Kingston to edema of the glottis. The disease is diagnosed by demonstrating the Reprint requests to: Dr. Peter G. functional absence in the serum of Fernandez, Faculty of medicine, Memorial the normal (a2-globulin) inhibitor of University of Newfoundland, St. John's, Nfld. AiC 5S7 the activated first component of com-
plement (C 1). Measurement of the serum concentration of one of the natural substrates of Cl, namely C4, is a reliable screening test: when the C4 concentration is low a direct test for Cl inhibitor will usually detect hereditary angioneurotic edema.2 The inheritance of this deficiency is autosomal dominant."4 Charcot-Marie Tooth disease was first described in 1866. It is characterized by degenerative changes in the central and peripheral nervous systems. Clinical features include selective muscle wasting, fasciculation,' pes cavus, and slow but progressive neurologic deficit.6 The disease may be inherited as an autosomal dominant, a recessive or an X-linked trait.7 These diseases are relatively rare, and there has been no previous report of their concurrent existence in the same individual or family. In this paper we describe a family (Fig. 1) in
FAMILY NONCO&FRlBLJ.ORY
® II.IJ HEREDITARY ANGIONEUROTIC EDEMA
V.ARlE-TOOTH DISEASE ..
PROPOSITUS
I
ii
y
0=9 FIG. 1-Pedigree of family with hereditary angioneurotic edema and Charcot-Marie-Tooth disease. CMA JOURNAL/SEPTEMBER 9, 1978/VOL. 119 455
which several members had one of Discussion the conditions each and three siblings All siblings of the propositus had had both. clinical signs and symptoms of CharClinical presentation and laboratory cot-Marie-Tooth disease, which was inherited from the mother. This disinvestigation ease may be transmitted in an autoA 21-year-old woman (lV,9) pre- somal dominant, a recessive or an sented with attacks of vomiting and X-linked pattern; the frequency of localized edema of the face and left clinical disease is highest with autohand that were precipitated by the somal dominant inheritance, interuse of oral contraceptives and re- mediate with X-linkage, and lowest mitted with discontinuation of the with autosomal recessive inheritance.7 drug. The muscles of the legs up Because the disease was transmitted to the lower third of the thighs were from one generation to the next and wasted and weak, the deep tendon affected both sexes the inheritance reflexes were diminished or absent, was considered to be autosomal and pes cavus was present bilaterally. dominant and not X-linked. the Two of her siblings (IV,10 and male-to-male transmission (11,5 to IV, 11) had clinical features of both 111,6) of the gene was even stronger diseases, and Charcot-Marie-Tooth evidence against X-linked inheritdisease was diagnosed in the other ance. Generally the most severe disthree siblings, the mother and three ease has been found with autosomal members of the mother's family. recessive inheritance.7 Serum concentrations of C4 and The specific molecular defect in Cl inhibitor were measured by radio- Charcot-Marie-Tooth disease has not immunodiffusion with a specific anti- yet been identified. Thompson,12 body against purified C42'8'9 and a specific anti-inhibitor antibody.10'11 Serum concentrations of glutamic oxaloacetic transaminase, lactic dehydrogenase,.aldolase and creatinine, and conduction velocities of the median nerve were measured in two of the women with Charcot-MarieTooth disease (IV,9 and IV,10). The propositus and the other members of the family were Caucasians from Kapuskasing, Ont.; there was no known history of consanguinity.
Results The pedigree in Fig. 1 shows autosomal dominant inheritance for hereditary angioneurotic edema on the paternal side of the family and for Charcot-Marie-Tooth disease on the maternal side. The serum concentrations of C4 and Cl inhibitor are given in Table I. The 10 members with clinical hereditary angioneurotic edema had low serum concentrations of C4 (as did 1 member without clinical evidence of the disease) and 3 members (IV,4, IV, 10 and IV, 11) showed a substantial decrease in the concentration of Cl inhibitor. The serum enzyme concentrations in the two women with Charcot-MarieTooth disease were within normal limits; however, the conduction velocities of the median nerve were decreased in both (Table H). 456 CMA JOURNAL/SEPTEMBER 9, 1978/VOL 119
however, has speculated about deficiencies in the fatty acid composition of nervous tissue resulting from the main genetic involvement in persons with the autosomal dominant trait. The disease is usually diagnosed clinically, and nerve conduction studies are invariably delayed; muscle biopsy and serum enzyme studies are singularly unhelpful, as we found in the two cases so investigated. Humberstone13 demonstrated that conduction in motor nerves was decreased before the onset of clinical features. The development of hereditary angioneurotic edema, on the other hand, can be explained by biochemical and cellular defects. It is currently thought that the disease affects not only the complement system, but also the kinin-generating and fibrinolytic systems.14 There are two forms of the disease: the autosomal doniinant type, constituting 85% of cases, in which the function of the Cl inhibitor is greatly reduced; and the form in which there are normal
'.Sandomigran® PIZOTYLI NE Prescribing information Dosage-The average maintenance dosage is 1 tablet (0.5 mg) t.i.d. A progressive dosage is recommended until the fifth day of therapy. Treatment should begin with 1(0.5 mg) tablet at bedtime (first two days), 1 tablet at noon, and at bedtime (next two days), and 1 tablet in the morning, at noon, and at bedtime (from the fifth day onward). The dosage range is 2 to 12 tablets (ito 6mg) per day. Since vascular headache is a paroxysmal but basically chronic disorder, treatment must extend over an adequate period of time in order to obtain maximal benefit. While some patients have responded rather quickly, most investigators agree that a four-week trial period should be instituted to determine the true efficacy of pizotyline in specific cases. The periodic nature of the disorder will have to be considered in determining when and for how long therapy should be maintained. Since some investigators have observed a change in headache pattern after several months of therapy, a drug-free interval is advisable to reassess the necessity of continuing treatment. The dosage should be reduced gradually during the last two weeks of each treatment course to avoid a "headache rebound." Composition-Each ivorycoloured, sugar-coated tablet contains 0.5 mg of pizotyline as the hydrogen malate. Side effects-Increased appetite, weight gain, and drowsiness are the most frequent side effects. An appropriate diet should be recommended by the physician for patients benefiting from the drug but gaining excessive weight. A gradual increase in the dosage of pizotyline is recommended to minimize or reduce the incidence of drowsiness. The following adverse effects have been observed less frequently in relation to the aforementioned reactions: fatigue, nausea, dizziness, headache, confusion, edema, hypotension depression, weakness, epigastric distress, dry mouth, nervousness, impotence and muscle pain. Warning and precautions-Since drowsiness may occur with pizotyline, sensitive patients should be cautioned against activities requiring rapid and precise response (i.e. driving an automobile or operating dangerous machinery) until their response to the drug has been determined. Since the effects of antihistamines can potentiate those of other drugs affecting the central nervous system, patients should be cautioned against drinking alcoholic beverages or taking hypnotics, sedatives, psychotherapeutic agents or other drugs with ONS depressant effects during pizotyline therapy. Since it is desirable to keep drug administration to a minimum during pregnancy, pizotyline should be given only when the benefits derived from treatment exceed the possible risks to mother and fetus. Some patients developed tolerance to pizotyline with prolonged use of the drug. An increase in dosage may overcome this tolerance. After prolonged use, hepatotoxic effects might occur and patients should be advised to report for adequate laboratory evaluation. Patients with diabetes, cardiovascular disease and known or suspected impaired renal or hepatic function should be given pizotyline with caution, and appropriate laboratory tests should be done at regular intervals. Lens opacities occured in two cases but did not appear to be drug-related. However, it is recommended that any impairment in vision be reported to the attending physician for further investigation. Contraindications-Glaucoma, pyloroduodenal obstruction, stenosing pyloric ulcer and predisposition to urinary retention. Pizotyline is also contraindicated in patients taking monoamine oxidase inhibitors and for patients who have a known sensitivity to the drug. Until further studies are completed, the drug is not recommended for children under the age of twelve. Supply-Bottles of 100 tablets. Full product information is available upon request.
or increased serum concentrations of antigenically identical but functionally deficient Cl . With both forms of the disease the affected individual is heterozygous.'6 It has been proposed that whereas the defect in the variant form is synthesis of a qualitatively abnormal Cl inhibitor, in the common form the defect is diminished synthesis of normal Cl inhibitor due either to a lack of one of the structural genes that codes for this protein or to a disorder of gene regulation . The serum concentration of C4 is persistently reduced in most patients with hereditary angioneurotic edema because the concentration of activated Cl is increased. The association of C4 concentrations and the development of clinical symptoms is complex, but in most persons with the autosomal dominant trait lower concentrations of C4 have been measured during attacks.14 This relation is difficult to demonstrate in the covariant form of the disease; however the propositus in our family and the two of her siblings who had both diseases did have lower C4 concentrations. We thank Dr. W.D. MacDiarmid of St. John's General Hospital and Memorial University of Newfoundland for valuable suggestions, Dr. W.E.M. Pryse-Phillips of St. John's General Hospital for carrying out the nerve conduction studies, Dr. A. Sheffer of Peter Bent Brigham Hospital in Boston and Dr. P.H. Kohier of the University of Colorado Medical Center in Denver for measuring the C4 and Cl inhibitor serum concentrations, and J. Tremblett for secretarial assistance.
BOOKS
References
continued from page 405
SANDOZ
5. HAASE GR, SHY GM: Pathological changes in muscle biopsies from patients with peroneal muscular atrophy. Brain 83: 631, 1960
vvy
SANDOZ (CANADA) LIMITED, DORvAL, QUEBEC
1. OSLER W: Hereditary angioneurotic edema. Am J Med Sci 95: 362, 1888 2. RUDDY 5, GIca.i I, SHEFFER A, et al:
The laboratory diagnosis of hereditary angioedema, in Proceedings of the 6th Congress of the International Association of A liergology, ROSEN B, RIcHTER M, SEHON A, et al (eds), Excerpta Medica Foundation, Amsterdam, 1968, pp 351-59 3. DONALDSON VH, EVANS RR: A bio-
chemical abnormality in hereditary angioneurotic edema. Absence of serum inhibitor of C'l-esterase. Am J Med 35: 37, 1963 4. ROSEN FS, CHARACHE P, PERSKY A,
et al: Hereditary angioneurotic edema: two genetic variants. Science 148: 957,
1965
458 CMA JOURNAL/SEPTEMBER 9, 1978/VOL 119
6. ENGLAND AC, DENNY-BROWN D: Se-
vere sensory changes and trophic disorders in peroneal muscular atrophy (Charcot-Marie-Tooth type). Arch Neurol Psychiatry 67: 1, 1952 7. Siu. H: Genetics and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet 6: 98, 1974 8. ROSENFELD SI, RUDDY 5, AUSTEN KF:
Structural polymorphism of the fourth component of human complement. I Clin Invest 48: 2283, 1969 9. KOHLER PF, PERCY I, CAMPTON WM,
et al: Hereditary angioedema and "familial" lupus erythematosus in identical twin boys. Am J Med 56: 406, 1974 10. GIGLI I, RUDDY 5, AUSTEN KF: The
stoichiometric measurement of the serum inhibitor of the first component of complement by the inhibition of immune hemolysis. J Immunol 100: 1154, 1968 11. RUDDY 5, GiGLI I, AUSTEN KF: The
complement system of man (four parts). N Engi J Med 287: 489, 545, 592, 642; 1972 12. THOMPSON RHS: Fatty acid metabolisin in multiple sclerosis. Biochem Soc Symp 35: 103, 1972 13. HUMBERSTONE PM: Nerve conduction studies in Charcot-Marie-Tooth disease. Acta Neurol Scand 48: 176, 1972 14. FRANK MM, GELFAND JA, ATKINSON
JP: Hereditary angioedema: the clinical syndrome and its management (NIH conference). Ann Intern Med 84: 580, 1976 15. SHOKEIR MHK: The genetics of hereditary angioedema: a hypothesis. Cliii Genet 4: 494, 1973 16. HADJIYANNAKI
K,
LACHMANN
PJ:
Hereditary angioedema: a review with particular reference to the pathogenesis and treatment. Clin Allergol 1: 221, 1971
DEPOT FLUPHENAZINES: TWELVE YEARS' EXPERIENCE. Edited by Frank J. Ayd, Jr. 160 pp. Illust. Ayd Medical Communications, Baltimore, 1978. $15, paperbound. ISBN 0-931858-00-3 EMERGENCY CARE HANDBOOK. How To Deal With People in Emergencies. Arthur R. Ciancutti. 100 pp. Technomic Publishing Co., Inc., Westport, CT; Natural Learning Center, San Anselmo, 1977. Price not stated. ISBN 7762-242-6 EVALUATIONS OF DRUG INTERACTIONS. 2nd ed. Supplement. Prepared by the American Pharmaceutical Association. 105 pp. American Pharmaceutical Association, Washington, D.C., 1978. $7, paperbound ($4 member rate) EXTENDING CANADIAN HEALTH INSURANCE: OPTIONS FOR PHARMACARE AND DENTICARE. R.G. Evans and M.F. Williamson. 267 pp. University of Toronto Press, Toronto, 1978. $12, paperbound. ISBN 0-8020-3353-9
continued on page 476
In one family two genetic diseases were transmitted as autosomal dominant traits; hereditary angioneurotic edema was inherited from the paternal side and Charcot-Marie-Tooth disease from the maternal side of the family. The conditions occurred separately in 8 and 11 members respectively and together (an exceedingly rare occurrence) in 3. Of six siblings, two girls and four boys, all had Charcot-Marie-Tooth disease, and three, the two girls and one of the boys, also had hereditary angioneurotic edema.
un oedeme angioneurotique hereditaire a ete transmis du c6te paternel et une amyotrophie peroniere de CharcotMarie-Tooth est venue du c6t6 matemel de Ia famille. Ces conditions sont survenues separement chez respective. ment 8 et 11 membres de Ia famille, et ensemble (un fait excessivement rare) chez 3. D'une fratrie de six, deux filles et quatre gar;ons, tous souffraient d'amyotrophie peroniere de Charcot-Marie-Tooth et trois, les deux filles et un des gar.ons, avaient aussi un oedeme angioneurotique.
Dans une famille deux maladies genetiques ont ete transmises comme des traits autosomiques dominants;
Osler1 in 1888 was the first to describe hereditary angioneurotic edema, a condition characterized by localized swelling of the skin on From *the faculty of medicine, Memorial various parts of the body, abdominal University of Newfoundland, St. John's, pain and laryngeal obstruction due and tthe department of medicine and Uhe division of genetics, department of pediatrics, Queen's University, Kingston to edema of the glottis. The disease is diagnosed by demonstrating the Reprint requests to: Dr. Peter G. functional absence in the serum of Fernandez, Faculty of medicine, Memorial the normal (a2-globulin) inhibitor of University of Newfoundland, St. John's, Nfld. AiC 5S7 the activated first component of com-
plement (C 1). Measurement of the serum concentration of one of the natural substrates of Cl, namely C4, is a reliable screening test: when the C4 concentration is low a direct test for Cl inhibitor will usually detect hereditary angioneurotic edema.2 The inheritance of this deficiency is autosomal dominant."4 Charcot-Marie Tooth disease was first described in 1866. It is characterized by degenerative changes in the central and peripheral nervous systems. Clinical features include selective muscle wasting, fasciculation,' pes cavus, and slow but progressive neurologic deficit.6 The disease may be inherited as an autosomal dominant, a recessive or an X-linked trait.7 These diseases are relatively rare, and there has been no previous report of their concurrent existence in the same individual or family. In this paper we describe a family (Fig. 1) in
FAMILY NONCO&FRlBLJ.ORY
® II.IJ HEREDITARY ANGIONEUROTIC EDEMA
V.ARlE-TOOTH DISEASE ..
PROPOSITUS
I
ii
y
0=9 FIG. 1-Pedigree of family with hereditary angioneurotic edema and Charcot-Marie-Tooth disease. CMA JOURNAL/SEPTEMBER 9, 1978/VOL. 119 455
which several members had one of Discussion the conditions each and three siblings All siblings of the propositus had had both. clinical signs and symptoms of CharClinical presentation and laboratory cot-Marie-Tooth disease, which was inherited from the mother. This disinvestigation ease may be transmitted in an autoA 21-year-old woman (lV,9) pre- somal dominant, a recessive or an sented with attacks of vomiting and X-linked pattern; the frequency of localized edema of the face and left clinical disease is highest with autohand that were precipitated by the somal dominant inheritance, interuse of oral contraceptives and re- mediate with X-linkage, and lowest mitted with discontinuation of the with autosomal recessive inheritance.7 drug. The muscles of the legs up Because the disease was transmitted to the lower third of the thighs were from one generation to the next and wasted and weak, the deep tendon affected both sexes the inheritance reflexes were diminished or absent, was considered to be autosomal and pes cavus was present bilaterally. dominant and not X-linked. the Two of her siblings (IV,10 and male-to-male transmission (11,5 to IV, 11) had clinical features of both 111,6) of the gene was even stronger diseases, and Charcot-Marie-Tooth evidence against X-linked inheritdisease was diagnosed in the other ance. Generally the most severe disthree siblings, the mother and three ease has been found with autosomal members of the mother's family. recessive inheritance.7 Serum concentrations of C4 and The specific molecular defect in Cl inhibitor were measured by radio- Charcot-Marie-Tooth disease has not immunodiffusion with a specific anti- yet been identified. Thompson,12 body against purified C42'8'9 and a specific anti-inhibitor antibody.10'11 Serum concentrations of glutamic oxaloacetic transaminase, lactic dehydrogenase,.aldolase and creatinine, and conduction velocities of the median nerve were measured in two of the women with Charcot-MarieTooth disease (IV,9 and IV,10). The propositus and the other members of the family were Caucasians from Kapuskasing, Ont.; there was no known history of consanguinity.
Results The pedigree in Fig. 1 shows autosomal dominant inheritance for hereditary angioneurotic edema on the paternal side of the family and for Charcot-Marie-Tooth disease on the maternal side. The serum concentrations of C4 and Cl inhibitor are given in Table I. The 10 members with clinical hereditary angioneurotic edema had low serum concentrations of C4 (as did 1 member without clinical evidence of the disease) and 3 members (IV,4, IV, 10 and IV, 11) showed a substantial decrease in the concentration of Cl inhibitor. The serum enzyme concentrations in the two women with Charcot-MarieTooth disease were within normal limits; however, the conduction velocities of the median nerve were decreased in both (Table H). 456 CMA JOURNAL/SEPTEMBER 9, 1978/VOL 119
however, has speculated about deficiencies in the fatty acid composition of nervous tissue resulting from the main genetic involvement in persons with the autosomal dominant trait. The disease is usually diagnosed clinically, and nerve conduction studies are invariably delayed; muscle biopsy and serum enzyme studies are singularly unhelpful, as we found in the two cases so investigated. Humberstone13 demonstrated that conduction in motor nerves was decreased before the onset of clinical features. The development of hereditary angioneurotic edema, on the other hand, can be explained by biochemical and cellular defects. It is currently thought that the disease affects not only the complement system, but also the kinin-generating and fibrinolytic systems.14 There are two forms of the disease: the autosomal doniinant type, constituting 85% of cases, in which the function of the Cl inhibitor is greatly reduced; and the form in which there are normal
'.Sandomigran® PIZOTYLI NE Prescribing information Dosage-The average maintenance dosage is 1 tablet (0.5 mg) t.i.d. A progressive dosage is recommended until the fifth day of therapy. Treatment should begin with 1(0.5 mg) tablet at bedtime (first two days), 1 tablet at noon, and at bedtime (next two days), and 1 tablet in the morning, at noon, and at bedtime (from the fifth day onward). The dosage range is 2 to 12 tablets (ito 6mg) per day. Since vascular headache is a paroxysmal but basically chronic disorder, treatment must extend over an adequate period of time in order to obtain maximal benefit. While some patients have responded rather quickly, most investigators agree that a four-week trial period should be instituted to determine the true efficacy of pizotyline in specific cases. The periodic nature of the disorder will have to be considered in determining when and for how long therapy should be maintained. Since some investigators have observed a change in headache pattern after several months of therapy, a drug-free interval is advisable to reassess the necessity of continuing treatment. The dosage should be reduced gradually during the last two weeks of each treatment course to avoid a "headache rebound." Composition-Each ivorycoloured, sugar-coated tablet contains 0.5 mg of pizotyline as the hydrogen malate. Side effects-Increased appetite, weight gain, and drowsiness are the most frequent side effects. An appropriate diet should be recommended by the physician for patients benefiting from the drug but gaining excessive weight. A gradual increase in the dosage of pizotyline is recommended to minimize or reduce the incidence of drowsiness. The following adverse effects have been observed less frequently in relation to the aforementioned reactions: fatigue, nausea, dizziness, headache, confusion, edema, hypotension depression, weakness, epigastric distress, dry mouth, nervousness, impotence and muscle pain. Warning and precautions-Since drowsiness may occur with pizotyline, sensitive patients should be cautioned against activities requiring rapid and precise response (i.e. driving an automobile or operating dangerous machinery) until their response to the drug has been determined. Since the effects of antihistamines can potentiate those of other drugs affecting the central nervous system, patients should be cautioned against drinking alcoholic beverages or taking hypnotics, sedatives, psychotherapeutic agents or other drugs with ONS depressant effects during pizotyline therapy. Since it is desirable to keep drug administration to a minimum during pregnancy, pizotyline should be given only when the benefits derived from treatment exceed the possible risks to mother and fetus. Some patients developed tolerance to pizotyline with prolonged use of the drug. An increase in dosage may overcome this tolerance. After prolonged use, hepatotoxic effects might occur and patients should be advised to report for adequate laboratory evaluation. Patients with diabetes, cardiovascular disease and known or suspected impaired renal or hepatic function should be given pizotyline with caution, and appropriate laboratory tests should be done at regular intervals. Lens opacities occured in two cases but did not appear to be drug-related. However, it is recommended that any impairment in vision be reported to the attending physician for further investigation. Contraindications-Glaucoma, pyloroduodenal obstruction, stenosing pyloric ulcer and predisposition to urinary retention. Pizotyline is also contraindicated in patients taking monoamine oxidase inhibitors and for patients who have a known sensitivity to the drug. Until further studies are completed, the drug is not recommended for children under the age of twelve. Supply-Bottles of 100 tablets. Full product information is available upon request.
or increased serum concentrations of antigenically identical but functionally deficient Cl . With both forms of the disease the affected individual is heterozygous.'6 It has been proposed that whereas the defect in the variant form is synthesis of a qualitatively abnormal Cl inhibitor, in the common form the defect is diminished synthesis of normal Cl inhibitor due either to a lack of one of the structural genes that codes for this protein or to a disorder of gene regulation . The serum concentration of C4 is persistently reduced in most patients with hereditary angioneurotic edema because the concentration of activated Cl is increased. The association of C4 concentrations and the development of clinical symptoms is complex, but in most persons with the autosomal dominant trait lower concentrations of C4 have been measured during attacks.14 This relation is difficult to demonstrate in the covariant form of the disease; however the propositus in our family and the two of her siblings who had both diseases did have lower C4 concentrations. We thank Dr. W.D. MacDiarmid of St. John's General Hospital and Memorial University of Newfoundland for valuable suggestions, Dr. W.E.M. Pryse-Phillips of St. John's General Hospital for carrying out the nerve conduction studies, Dr. A. Sheffer of Peter Bent Brigham Hospital in Boston and Dr. P.H. Kohier of the University of Colorado Medical Center in Denver for measuring the C4 and Cl inhibitor serum concentrations, and J. Tremblett for secretarial assistance.
BOOKS
References
continued from page 405
SANDOZ
5. HAASE GR, SHY GM: Pathological changes in muscle biopsies from patients with peroneal muscular atrophy. Brain 83: 631, 1960
vvy
SANDOZ (CANADA) LIMITED, DORvAL, QUEBEC
1. OSLER W: Hereditary angioneurotic edema. Am J Med Sci 95: 362, 1888 2. RUDDY 5, GIca.i I, SHEFFER A, et al:
The laboratory diagnosis of hereditary angioedema, in Proceedings of the 6th Congress of the International Association of A liergology, ROSEN B, RIcHTER M, SEHON A, et al (eds), Excerpta Medica Foundation, Amsterdam, 1968, pp 351-59 3. DONALDSON VH, EVANS RR: A bio-
chemical abnormality in hereditary angioneurotic edema. Absence of serum inhibitor of C'l-esterase. Am J Med 35: 37, 1963 4. ROSEN FS, CHARACHE P, PERSKY A,
et al: Hereditary angioneurotic edema: two genetic variants. Science 148: 957,
1965
458 CMA JOURNAL/SEPTEMBER 9, 1978/VOL 119
6. ENGLAND AC, DENNY-BROWN D: Se-
vere sensory changes and trophic disorders in peroneal muscular atrophy (Charcot-Marie-Tooth type). Arch Neurol Psychiatry 67: 1, 1952 7. Siu. H: Genetics and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet 6: 98, 1974 8. ROSENFELD SI, RUDDY 5, AUSTEN KF:
Structural polymorphism of the fourth component of human complement. I Clin Invest 48: 2283, 1969 9. KOHLER PF, PERCY I, CAMPTON WM,
et al: Hereditary angioedema and "familial" lupus erythematosus in identical twin boys. Am J Med 56: 406, 1974 10. GIGLI I, RUDDY 5, AUSTEN KF: The
stoichiometric measurement of the serum inhibitor of the first component of complement by the inhibition of immune hemolysis. J Immunol 100: 1154, 1968 11. RUDDY 5, GiGLI I, AUSTEN KF: The
complement system of man (four parts). N Engi J Med 287: 489, 545, 592, 642; 1972 12. THOMPSON RHS: Fatty acid metabolisin in multiple sclerosis. Biochem Soc Symp 35: 103, 1972 13. HUMBERSTONE PM: Nerve conduction studies in Charcot-Marie-Tooth disease. Acta Neurol Scand 48: 176, 1972 14. FRANK MM, GELFAND JA, ATKINSON
JP: Hereditary angioedema: the clinical syndrome and its management (NIH conference). Ann Intern Med 84: 580, 1976 15. SHOKEIR MHK: The genetics of hereditary angioedema: a hypothesis. Cliii Genet 4: 494, 1973 16. HADJIYANNAKI
K,
LACHMANN
PJ:
Hereditary angioedema: a review with particular reference to the pathogenesis and treatment. Clin Allergol 1: 221, 1971
DEPOT FLUPHENAZINES: TWELVE YEARS' EXPERIENCE. Edited by Frank J. Ayd, Jr. 160 pp. Illust. Ayd Medical Communications, Baltimore, 1978. $15, paperbound. ISBN 0-931858-00-3 EMERGENCY CARE HANDBOOK. How To Deal With People in Emergencies. Arthur R. Ciancutti. 100 pp. Technomic Publishing Co., Inc., Westport, CT; Natural Learning Center, San Anselmo, 1977. Price not stated. ISBN 7762-242-6 EVALUATIONS OF DRUG INTERACTIONS. 2nd ed. Supplement. Prepared by the American Pharmaceutical Association. 105 pp. American Pharmaceutical Association, Washington, D.C., 1978. $7, paperbound ($4 member rate) EXTENDING CANADIAN HEALTH INSURANCE: OPTIONS FOR PHARMACARE AND DENTICARE. R.G. Evans and M.F. Williamson. 267 pp. University of Toronto Press, Toronto, 1978. $12, paperbound. ISBN 0-8020-3353-9
continued on page 476
