deaf-mutism and type-ii hyperlipoproteinqmia

892

asymptomatic women with antitrypsin deficiency a low

diffusing capacity (co), together with decreased perfusion inthe lower zones on lung scanning. Whether or not thisrepresents a panacinar emphysema is unknown, and canonly be established by post-mortem examinations. 3,4,7

I was unable to show an increased frequency of chronicobstructive lung disease in the 60 or heterozygotes in myseries. Other workers 10,11 have suggested the opposite, buttheir findings could be due to selection and inadequatecontrols. Since the gene for «1-antitrypsin deficiency hasa relatively high incidence (0-024 in a Swedish population),3presumably people with intermediate levels can exhibitchronic lung disease without the association being statistic-ally significant. Careful studies have also shown that such

people show a broad spectrum of lung changes completelydifferent from the panacinar emphysema of homozygousantitrypsin deficiency.9 9 A priori it seems unlikely thatclinically manifest disease would occur in carriers. Experi-ence from studies of other recessively inherited conditionsdoes not support such a hypothesis.My original suggestion that «1-antitrypsin protects the

lung against the destructive action of various proteolyticenzymes has been correctly quoted but never proved. Both«1-antitrypsin and CX2- macroglobulin inhibit elastase as wellas trypsin.12 CX2 macroglobulin concentration is raised in

patients with antitrypsin deficiency whether or not there aresigns of lung disease.13 Only follow-up studies of asympto-matic men with homozygous «1-antitrypsin deficiency canincrease the knowledge of the causal pathophysiologicalmechanisms in this syndrome. Adequate documentation ofthese individuals is thus very important. Owing to its shorthalf-life 14 (about 4 days), «1-antitrypsin would seem to be oflittle potential therapeutic value, but administration of

synthetic protease inhibitors with similar biological activityshould, with long-term clinical trial, and a control group,answer the question of whether antitrypsin deficiency per seis the cause of panacinar emphysema. Such investigationswould also be of great value in the study of the naturalhistory of emphysema and in assessment of the differenttypes of lung-function tests for in early diagnosis.

STEN ERIKSSON.

Department of Medicine,Central Hospital,

Våsterås, Sweden.

DEAF-MUTISM AND TYPE-II

HYPERLIPOPROTEINÆMIA

SIR,-Since Penred 15 described the association betweendeaf-mutism and goitre, congenital hearing losses havebeen related to many other defects. A review of hereditarydeafness by Konigsmark 16 lists over 60 varieties of deafness,of which about 50 have associations with defects in othersystems. Post-mortem observations on one patient who wasdeaf and dumb, and subsequent investigations on herdaughter, have brought to light, we believe, an as yetundescribed association of deaf mutism with familial

type-li hyperlipoproteintmia (p-lipoproteinasmia).Patient 1A 67-year-old deaf-mute patient was brought to the

hospital with some weeks’ history of left-sided chest pain.She had also become less active. On the evening ofadmission she vomited several times. She lived only 12hours after admission and at necropsy (December, 1966)she had generalised atherosclerosis with thrombosis of theanterior descending branch of the left coronary artery and11. Kueppers, F., Fallat, R., Larsson, R. K. Science, N.Y. 1969, 165,

899.12. Heimberger, N., Haupt, H. Klin. Wschr. 1966, 44, 1196.13. Ganrot, P. O., Laurell, C.-B., Eriksson, S. Scand. J. clin. Lab.

Invest. 1967, 19, 205.14. Kueppers, F. Fallat, R. J. Clin. chim. Acta, 1969, 24, 401.15. Penred, V. Lancet, 1896, ii, 532.16. Konigsmark, B. W. New Engl. J. Med. 1969, 281, 713, 774, 827.

anteroseptal myocardial infarction. In addition, there wasobvious enlargement of both her Achilles tendons and of theextensor tendon of the left third finger, and a small swellingin the skin of the left elbow. Sections of these showedsubcutaneous or tendinous deposition of cholesterol withgiant-cell inflammatory response and infiltration by foamymacrophages. The thyroid was enlarged (48 g.) and showedlymphocytic thyroiditis. The kidneys were unremarkable.A post-mortem serum-cholesterol was 463 mg. per 100 ml.Patient 2

This woman was the daughter of patient 1, and was alsodeaf and dumb but mentally alert. She was admitted to the

hospital in November, 1959, with proptosis of the left eye ofabout 2 years’ duration. In the orbit, a tumour, attached tobone, was found and excised. It presented large foamymacrophages, cholesterol with foreign body reaction, andsome bony spicules. A diagnosis of xanthoma was madeand the patient was discharged. Almost 10 years later inNovember, 1969, the patient, now 39 years of age, returnedwith recurrence of proptosis of the left eye. A tumour withhistological features identical to those found 10 years beforewas removed. Fasting serum-cholesterol was 421 mg. per100 ml. The serum was clear. The lipoproteins wereseparated by paper electrophoresis, using a standard

method and an intense p-band was present. There wassome increase in intensity of the a-band. Chylomicrons andpre-p-lipoprotein were absent. Fasting blood-glucose was91 mg. per 100 ml., triglycerides 65 mg. per 100 ml., uricacid 4-0 mg. per 100 ml., and blood-urea-nitrogen 14-0 mg.per ml. Serum-proteins were 7-2 g. per 100 ml. (albumin3-6 g. per 100 ml., globulin 3-6 g. per 100 ml.) and protein-bound iodine 5-6 µg. per 100 ml. Like her mother, she hadgreatly thickened Achilles tendons. The kindred ofpatients 1 and 2 are shown in the accompanying figuie.There was no known consanguinity.

Since the sister of patient 2 had normal hearing, we maypresume that the genes responsible for deafness in patient1’s husband and in herself were different and that patient2’s sister, who has 9 hearing children, is free of any hearingstigma from either father or mother. Since patient 2 had allthe features of heterozygous type-il hyperlipoproteinaemia,17as did her mother, it is not unreasonable to suppose that

they both carried the single defective gene.None of patient 2’s children has thickened ankles and

none is deaf, which would make one suspect that the hyper-lipoproteinaemia and the deafness are linked; a fortuitousassociation is possible but less likely.

Unfortunately it has not proved possible to examine thechildren of patient 2, nor her sister or surviving aunt.

However, the association of familial type-il hyperlipo-proteinasmia and deafness in mother and daughter is

apparently unique, and we hope there will be opportunitiesto study this family further.

STANLEY S. RAPHAELT. A. HYDE.

Department of Pathology,Hotel-Dieu of St. Joseph,Windsor 14, Ontario, Canada.

17. Fredrickson, D. S., Levy, R. I., Lees, S. R. ibid. 1967, 276, 34, 94,148, 215, 273.