J Neurol (1992) 239 : 351-353
Journal of
Neurology © Springer-Verlag 1992
Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy Alessandro Fiila 1, Giuseppe De Michele 1, Roberto Marconi 2, Luigi Bucci 2, Carmine Carillo 2, Anna Elisa Castellano 2, Lucio Iorio 2, Claudio Kniahynicki:, Francesco Rossi 2, and Giuseppe Campanella 1 1Department of Neurology, Second School of Medicine, University of Naples, Via Pansini, 5, 1-80131 Naples, Italy :Neurological Institute "Sanatrix", Venafro, Italy Received August 2, 1991 / Received in revised form November 18, 1991 / Accepted December 2, 1991
Summary. A n epidemiological survey of hereditary ataxias and paraplegias was c o n d u c t e d in Molise, a region of Italy (335,211 inhabitants on 1 J a n u a r y 1989). Total prevalence was 7.5 × 10 -5 inhabitants (95% confidence limits 4.8-11.1). T h e r e were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 a u t o s o m a l d o m i n a n t and 7 a u t o s o m a l recessive cases). T h e r e was no patient with a u t o s o m a l d o m i n a n t cerebellar ataxia.
Key words: E p i d e m i o l o g y - H e r e d i t a r y ataxias - H e r e d itary spastic paraplegias
Introduction
Isernia) and into 136 districts (Fig. 1). It covers an area of 4,438 km a with a resident population of 335,211 on 1 January 1989.
Diagnostic criteria We considered early onset progressive ataxia, recessive inheritance or sporadic occurrence essential for the diagnosis of Friedreich's disease (FD), early onset cerebellar ataxia with retained tendon reflexes (EOCA) and ataxia-telangiectasia (AT). Additional diagnostic criteria for FD were lower limb areflexia and in the index case at least one of the following signs: dysarthria, extensor plantar response, echocardiographic evidence of hypertrophic cardiomyopathy [3]. In EOCA patients knee jerks were always present, usually associated with dysarthria and pyramidal weakness [4]. In AT patients the ataxia was associated with telangiectasias, increased serum level of alpha-fetoprotein and oculomotor apraxia. Diagnostic criteria for HSP were progressing spastic gait with brisk knee jerks and evidence, by history or clinical examination, of a similar disease in the family. The presence of increased knee
T h e hereditary ataxias ( H A ) are a g r o u p of rare diseases characterized by d e g e n e r a t i o n of the cerebellum, brain stem and spinal cord. Hereditary spastic paraplegias (HSP) are a related group of diseases. In both conditions inheritance m a y be a u t o s o m a l d o m i n a n t , a u t o s o m a l recessive or, rarely, X-linked. Epidemiological surveys of H A and H S P have app e a r e d in the literature, but the use of i n a p p r o p r i a t e classifications and the lack of accurate diagnostic criteria w e a k e n e d m o s t of them. T h e aim of this study was to determine the prevalence of H A and H S P in Molise, a region of Italy, using the classification of those forms recently p r o p o s e d by H a r d ing [5], which is n o w widely accepted.
Materials and methods Study population The region of Molise is located at the border between central and southern Italy and is divided into two provinces (Campobasso and
Correspondence to: A. Filla
Fig. 1. The region of Molise
352 jerks associated with extensor plantar response, spasticity or pyramidal weakness was sufficient for diagnosis in secondary asymptomatic cases. Diagnostic criteria for other forms of HA which we did not find in this study were essentially those described by Harding [5].
Patient ascertainment and data collection In order to locate patients a call-letter-call survey was designed, Among the 1,222 physicians registered in the College of Physicians of Molise, 847 (neurologists, general practitioners, paediatricians, internists, orthopaedist, ophthalmologists) were considered for the survey. The physicians were telephoned and informed about the aim of the study and confidentiality of information and all agreed to participate in the survey. They were questioned following a standardized schedule devised to collect all patients with a possible diagnosis of HA or HSP. They subsequently received a letter with the same questions, and finally another telephone call to collect names of patients with tentative diagnoses of HA and HSP. The files from the only department of neurology and from the five rehabilitation centres were checked from 1979 to the present. All patients with a tentative diagnosis of HA or HSP were examined by a neurologist (G.C., G.D.M., A.F.). When possible, patients who satisfied the above diagnostic criteria underwent neurophysiological and neuroimaging studies. Hexosaminidases A and B, vitamin E and sex hormones were assayed in selected cases. Patients were included in the study if they were residents of Molise on prevalence day. Relatives suspected of having a similar disease and, when possible, the other first-degree relatives were examined.
Results Seventy-nine patients were examined. T w o w o m e n , o n e with F D and the o t h e r with E O C A , and two sisters with H S P of a u t o s o m a l recessive type were excluded b e c a u s e they were not resident in Molise at the time of the study. Fifty of t h e m were excluded since they failed to fulfil the diagnostic criteria w h e n examined. N o n e of t h e m had a suspected diagnosis of H A or H S P . I n 21 spastic paraplegia was the p r o m i n e n t feature, in the majority of t h e m due to cerebral palsy. Six patients were ataxic, the m o s t c o m m o n causes being chronic alcoholism and phenytoin treatment. T w e n t y - t h r e e , neither paraparetic n o r ataxic, h a d a variety of different neurological or muscular disorders. Twenty-five patients w e r e included in the study. T h r e e of t h e m w e r e s e c o n d a r y cases (2 recessive and 1 d o m i n a n t H S P ) .
Seven patients (3 males and 4 females) with F D were seen. Consanguinity was present in four of six marriages. O n s e t age was 13.1, SD 4.8 years and age at the time of the study was 31.9, SD 13.3 years. T h e s e patients' clinical features were not different f r o m those usually f o u n d in the disease [2, 3]. Five male patients f r o m four families had E O C A . N o c o n s a n g u i n e o u s marriage was reported. O n s e t age was 12.0, SD 4.5 years and age at the time of the study was 27.6, SD 10.2 years. F o u r patients (3 males and 1 female) with A T were seen. Consanguinity was present in two of three marriages. O n s e t age was 2.3, SD 0.5 years and age at the time of the study was 21.8, SD 4.9 years. Nine patients (6 males and 3 females) f r o m five families with H S P were seen. O n s e t age was 20.9, SD 11.2 years and age at the time of the study was 37.8, SD 18.5 years. In one family the father and one child were affected. In the o t h e r four families autosomal recessive inheritance was apparent. T h r e e of these families (two singletons and o n e triplet) b e l o n g e d to the same large inbred pedigree and the parents of two of t h e m were consanguineous. In the two affected sibs of the fourth family a m o d e r a t e l y low I Q was present. Clinical findings were those of " p u r e " spastic paraplegia in the other four families. Total prevalence of H A and H S P in Molise was 7.5 x 10 -5 (95% confidence limits 4.8-11.1). Prevalence by sex and age is shown in Table 1. Prevalence standardized by age and sex on the Italian p o p u l a t i o n on 1 J a n u a r y 1989 was 7.8 × 10 -5. E v e n t h o u g h the male to female ratio was 2.2, sex difference was n o t significant (chi s q u a r e = 2 . 5 6 ) . T h e highest prevalence values were f o u n d in the third decade. T h e prevalence of individual diseases was 2.1 × 10 .5 (95% confidence limits 0 . 8 - 4 . 3 ) for F D , 1.5 (0.5-3.5) for E O C A , 1.2 (0.3-3.1) for A T and 2.7 (1.2-5.1) for H S P .
Discussion In the present study strict diagnostic criteria were applied. In o r d e r to m a k e our ascertainment as complete as possible, we chose a limited area and population. Since it was impossible to p e r f o r m a d o o r - t o - d o o r survey, we not
Table 1. Prevalence of hereditary ataxias and spastic paraplegias by sex and age in Molise Age groups
Population
(years)
Males
Females
Total
No. of cases
Prevalence x 10.5
Males
Males
Females
Total
Females Total
0- 9 10-19 20-29 30-39 40-49 50-59 60->
19264 24535 27367 22791 18467 19502 31970
18399 23502 26808 21996 18174 20991 41445
37663 48037 54175 44787 36641 40493 73415
0 4 7 2 3 0 1
0 1 2 1 2 2 0
0 5 9 3 5 2 1
0 16.3 25.6 8.8 16.2 0 3.1
0 4.3 7.5 4.5 11.0 9.5 0
0 10.4 16.6 6.7 13.6 4.9 1.4
Total
163 896
171315
335 211
17
8
25
10.4
4.7
7.5
353 Table 2. Prevalence of hereditary ataxias and spastic paraplegias. EOCA, Early onset cerebellar ataxia with retained tendon reflexes
Sweden [10] Western Norway [11]a Benghazi (Libya) [12] Turin (Italy) [1] Zealand (Denmark) [13]b Cantabria (Spain) [7] Present study
1.2 1.0 0.4 1.0 0.8 4.7 2.1
1.0 0.5 2.3 1.5
0 0 1.2
11.9 2.1 c 1.3c 0.5 9.6 2.7
2.0 22.1 4.8 6.1 5.8 20.2 7.5
a Prevalence ratios were corrected by estimation of ascertainment probability. The actual number of cases was 5 for Friedreich's disease (FD), 31 for hereditary spastic paraplegia (HSP) and 68 for all hereditary ataxias (HA) and HSP in a population of 725,000 inhabitants b Prevalence rates were estimated as the product of incidence density and duration of disease in a 10- to 50-year-old population. The actual number of cases was 10 for FD, 22 HSP and 59 for all HA and HSP in a population of 1,179,000 inhabitants ° Sporadic cases of spastic paraplegia were also included
only e x a m i n e d records f r o m hospitals and rehabilitation centres but interviewed general pratictioners and specialists w h o were likely to have patients with H A and H S P . In Italy free medical care and g o v e r n m e n t financial assistance for the disabled bring patients to medical attention. Table 2 summarizes the m o s t relevant prevalence studies on H A and H S P . Most of t h e m give prevalence ratios close to ours. H i g h e r prevalence values were rep o r t e d in two studies [7, 11]. Skre [11] d o u b l e d his actual value, correcting it by ascertainment probability. T h e high prevalence ratio f o u n d by Polo et al. [7] might be due, in recessive forms, to the general p o p u l a t i o n ' s high consanguinity and, in d o m i n a n t forms, to the large n u m ber o f s e c o n d a r y cases. T h e prevalence ratio w h e n only index cases were considered was 9.4 × 10 -5. A lower prevalence ratio was f o u n d by SjOgren [10], but the aut h o r himself considered his estimate to be 50% of the actual ratio. O u r prevalence ratio for F D is slightly higher than m o s t values r e p o r t e d in the literature and lower than that f o u n d by Polo et al. [7]. A prevalence ratio of 1.2 x 10 .5 was recently f o u n d in n o r t h - w e s t e r n Italy [6]. G i v e n a disease d u r a t i o n of 30 years and a n o r m a l life expectancy of 70 years, we can estimate f r o m o u r prevalence ratio a birth incidence of 4.9 x 10 .5 (2.1 × 10 .5 x 70/30) [14]. This value is very close to the 4.5 × 10 .5 estimated f r o m the f r e q u e n c y o f first-cousin marriages in Italy [8] and higher than the 2.8 × 10 .5 f o u n d during the period 1948-1964 in n o r t h - w e s t e r n Italy [6]. T h e E O C A prevalence ratio in Molise is intermediate a m o n g r e p o r t e d values. A s far as A T is c o n c e r n e d , s o m e surveys [7, 12] r e p o r t e d no case and others [1, 10, 11, 13] gave no figures. Sedgwick and B o d e r [9] r e p o r t e d a pre-
valence of 1.5 × 10 .5 in the 5- to 18-year-old p o p u l a t i o n of Los Angeles. H S P prevalence ratios higher than ours have b e e n r e p o r t e d by Skre [11], w h o corrected his data by ascertainment probability, and by Polo et al. [7]. In this last survey only 9 patients were p r o b a n d s , whereas the o t h e r 40 were s e c o n d a r y cases. D o m i n a n t H S P families o u t n u m b e r the recessive in some studies [7, 11], while the reverse o c c u r r e d in the L i b y a n study [12] and ours.
In conclusion, F D is the m o s t f r e q u e n t f o r m of H A in Molise, accounting for 44% of cases; E O C A and A T follow in that order; no d o m i n a n t f o r m of H A was found; in H S P also there was a p r e p o n d e r a n c e of recessive cases.
Acknowledgement. This work was supported by grants from CNR (no. 89.0327) and the Italian Ministry of Health.
References
1. Brignolio F, Leone M, Tribolo A, Rosso MG, Meineri P, Schiffer D (1986) Prevalence of hereditary ataxias and paraplegias in the province of Torin, Italy. Ital J Neurol Sci 7:431-435 2. Campanella G, Filla A, De Falco FA, Mansi D, Durivage A, Barbeau A (1980) Friedreich's ataxia in the south of Italy: a clinical and biochemical survey of 23 patients. Can J Neurol Sci 7 : 351-358 3. Filla A, De Michele G, Caruso G, Marconi R, Campanella G (1990) Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients. J Neurol 237:345-351 4. Harding AE (1981) Early onset cerebellar ataxia with retained tendon reflexes: a clinical and genetic study of a disorder distinct from Friedreich's ataxia. J Neurol Neurosurg Psychiatry 44: 871-883 5. Harding AE (1984) The hereditary ataxias and related disorders. Churchill Livingstone, Edinburgh 6. Leone M, Brignolio F, Rosso MG, Curtoni ES, Moroni A, Tribolo A, Schiffer D (1990) Friedreich's ataxia: a descriptive epidemiological study in an Italian population. Clin Genet 38 : 161-169 7. Polo GM, Calleja J, Combarros O, Berciano J (1991) Hereditary ataxias and paraplegias in Cantabria, Spain. An epidemiological and clinical study. Brain 114:855-866 8. Romeo G, Menozzi P, Ferlini A, Fadda S, Di Donato S, Uziel G, Lucci B, Capodaglio L, Filla A, Campanella G (1983) Incidence of Friedreich's ataxia in Italy estimated from consanguineous marriages. Am J Hum Genet 35 : 523-529 9. Sedgwick RP, Boder E (1972) Ataxia-telangiectasia. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 14. North-Holland, Amsterdam, pp 267-339 10. Sj6gren T (1943) Klinische und erbbiologische Untersuchungen tiber die Heredoataxien. Acta Psychiatr Neurol Scand 27 [Suppl] : 1-200 11. Skre H (1980) Epidemiology of spinocerebellar degeneration in Western Norway: hereditary ataxias. In: Sobue I (ed) Spinocerebellar degenerations. University of Tokyo Press, Tokyo, pp 103-119 12. Sridharan R, Radhakrishnan K, Ashok PP, Mousa ME (1985) Prevalence and pattern of spinocerebellar degeneration in Northeastern Libya. Brain 108:831-843 13. Werdelin L (1986) Hereditary ataxias. Occurrence and clinical features. Acta Neurol Scand 73 [Suppl 106] : 1-124 14. Winter RM, Harding AE, Baraitser M, Bravery MB (1981) Intrafamilial correlation in Friedreich's ataxia. Clin Genet 20 : 419-427
Journal of
Neurology © Springer-Verlag 1992
Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy Alessandro Fiila 1, Giuseppe De Michele 1, Roberto Marconi 2, Luigi Bucci 2, Carmine Carillo 2, Anna Elisa Castellano 2, Lucio Iorio 2, Claudio Kniahynicki:, Francesco Rossi 2, and Giuseppe Campanella 1 1Department of Neurology, Second School of Medicine, University of Naples, Via Pansini, 5, 1-80131 Naples, Italy :Neurological Institute "Sanatrix", Venafro, Italy Received August 2, 1991 / Received in revised form November 18, 1991 / Accepted December 2, 1991
Summary. A n epidemiological survey of hereditary ataxias and paraplegias was c o n d u c t e d in Molise, a region of Italy (335,211 inhabitants on 1 J a n u a r y 1989). Total prevalence was 7.5 × 10 -5 inhabitants (95% confidence limits 4.8-11.1). T h e r e were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 a u t o s o m a l d o m i n a n t and 7 a u t o s o m a l recessive cases). T h e r e was no patient with a u t o s o m a l d o m i n a n t cerebellar ataxia.
Key words: E p i d e m i o l o g y - H e r e d i t a r y ataxias - H e r e d itary spastic paraplegias
Introduction
Isernia) and into 136 districts (Fig. 1). It covers an area of 4,438 km a with a resident population of 335,211 on 1 January 1989.
Diagnostic criteria We considered early onset progressive ataxia, recessive inheritance or sporadic occurrence essential for the diagnosis of Friedreich's disease (FD), early onset cerebellar ataxia with retained tendon reflexes (EOCA) and ataxia-telangiectasia (AT). Additional diagnostic criteria for FD were lower limb areflexia and in the index case at least one of the following signs: dysarthria, extensor plantar response, echocardiographic evidence of hypertrophic cardiomyopathy [3]. In EOCA patients knee jerks were always present, usually associated with dysarthria and pyramidal weakness [4]. In AT patients the ataxia was associated with telangiectasias, increased serum level of alpha-fetoprotein and oculomotor apraxia. Diagnostic criteria for HSP were progressing spastic gait with brisk knee jerks and evidence, by history or clinical examination, of a similar disease in the family. The presence of increased knee
T h e hereditary ataxias ( H A ) are a g r o u p of rare diseases characterized by d e g e n e r a t i o n of the cerebellum, brain stem and spinal cord. Hereditary spastic paraplegias (HSP) are a related group of diseases. In both conditions inheritance m a y be a u t o s o m a l d o m i n a n t , a u t o s o m a l recessive or, rarely, X-linked. Epidemiological surveys of H A and H S P have app e a r e d in the literature, but the use of i n a p p r o p r i a t e classifications and the lack of accurate diagnostic criteria w e a k e n e d m o s t of them. T h e aim of this study was to determine the prevalence of H A and H S P in Molise, a region of Italy, using the classification of those forms recently p r o p o s e d by H a r d ing [5], which is n o w widely accepted.
Materials and methods Study population The region of Molise is located at the border between central and southern Italy and is divided into two provinces (Campobasso and
Correspondence to: A. Filla
Fig. 1. The region of Molise
352 jerks associated with extensor plantar response, spasticity or pyramidal weakness was sufficient for diagnosis in secondary asymptomatic cases. Diagnostic criteria for other forms of HA which we did not find in this study were essentially those described by Harding [5].
Patient ascertainment and data collection In order to locate patients a call-letter-call survey was designed, Among the 1,222 physicians registered in the College of Physicians of Molise, 847 (neurologists, general practitioners, paediatricians, internists, orthopaedist, ophthalmologists) were considered for the survey. The physicians were telephoned and informed about the aim of the study and confidentiality of information and all agreed to participate in the survey. They were questioned following a standardized schedule devised to collect all patients with a possible diagnosis of HA or HSP. They subsequently received a letter with the same questions, and finally another telephone call to collect names of patients with tentative diagnoses of HA and HSP. The files from the only department of neurology and from the five rehabilitation centres were checked from 1979 to the present. All patients with a tentative diagnosis of HA or HSP were examined by a neurologist (G.C., G.D.M., A.F.). When possible, patients who satisfied the above diagnostic criteria underwent neurophysiological and neuroimaging studies. Hexosaminidases A and B, vitamin E and sex hormones were assayed in selected cases. Patients were included in the study if they were residents of Molise on prevalence day. Relatives suspected of having a similar disease and, when possible, the other first-degree relatives were examined.
Results Seventy-nine patients were examined. T w o w o m e n , o n e with F D and the o t h e r with E O C A , and two sisters with H S P of a u t o s o m a l recessive type were excluded b e c a u s e they were not resident in Molise at the time of the study. Fifty of t h e m were excluded since they failed to fulfil the diagnostic criteria w h e n examined. N o n e of t h e m had a suspected diagnosis of H A or H S P . I n 21 spastic paraplegia was the p r o m i n e n t feature, in the majority of t h e m due to cerebral palsy. Six patients were ataxic, the m o s t c o m m o n causes being chronic alcoholism and phenytoin treatment. T w e n t y - t h r e e , neither paraparetic n o r ataxic, h a d a variety of different neurological or muscular disorders. Twenty-five patients w e r e included in the study. T h r e e of t h e m w e r e s e c o n d a r y cases (2 recessive and 1 d o m i n a n t H S P ) .
Seven patients (3 males and 4 females) with F D were seen. Consanguinity was present in four of six marriages. O n s e t age was 13.1, SD 4.8 years and age at the time of the study was 31.9, SD 13.3 years. T h e s e patients' clinical features were not different f r o m those usually f o u n d in the disease [2, 3]. Five male patients f r o m four families had E O C A . N o c o n s a n g u i n e o u s marriage was reported. O n s e t age was 12.0, SD 4.5 years and age at the time of the study was 27.6, SD 10.2 years. F o u r patients (3 males and 1 female) with A T were seen. Consanguinity was present in two of three marriages. O n s e t age was 2.3, SD 0.5 years and age at the time of the study was 21.8, SD 4.9 years. Nine patients (6 males and 3 females) f r o m five families with H S P were seen. O n s e t age was 20.9, SD 11.2 years and age at the time of the study was 37.8, SD 18.5 years. In one family the father and one child were affected. In the o t h e r four families autosomal recessive inheritance was apparent. T h r e e of these families (two singletons and o n e triplet) b e l o n g e d to the same large inbred pedigree and the parents of two of t h e m were consanguineous. In the two affected sibs of the fourth family a m o d e r a t e l y low I Q was present. Clinical findings were those of " p u r e " spastic paraplegia in the other four families. Total prevalence of H A and H S P in Molise was 7.5 x 10 -5 (95% confidence limits 4.8-11.1). Prevalence by sex and age is shown in Table 1. Prevalence standardized by age and sex on the Italian p o p u l a t i o n on 1 J a n u a r y 1989 was 7.8 × 10 -5. E v e n t h o u g h the male to female ratio was 2.2, sex difference was n o t significant (chi s q u a r e = 2 . 5 6 ) . T h e highest prevalence values were f o u n d in the third decade. T h e prevalence of individual diseases was 2.1 × 10 .5 (95% confidence limits 0 . 8 - 4 . 3 ) for F D , 1.5 (0.5-3.5) for E O C A , 1.2 (0.3-3.1) for A T and 2.7 (1.2-5.1) for H S P .
Discussion In the present study strict diagnostic criteria were applied. In o r d e r to m a k e our ascertainment as complete as possible, we chose a limited area and population. Since it was impossible to p e r f o r m a d o o r - t o - d o o r survey, we not
Table 1. Prevalence of hereditary ataxias and spastic paraplegias by sex and age in Molise Age groups
Population
(years)
Males
Females
Total
No. of cases
Prevalence x 10.5
Males
Males
Females
Total
Females Total
0- 9 10-19 20-29 30-39 40-49 50-59 60->
19264 24535 27367 22791 18467 19502 31970
18399 23502 26808 21996 18174 20991 41445
37663 48037 54175 44787 36641 40493 73415
0 4 7 2 3 0 1
0 1 2 1 2 2 0
0 5 9 3 5 2 1
0 16.3 25.6 8.8 16.2 0 3.1
0 4.3 7.5 4.5 11.0 9.5 0
0 10.4 16.6 6.7 13.6 4.9 1.4
Total
163 896
171315
335 211
17
8
25
10.4
4.7
7.5
353 Table 2. Prevalence of hereditary ataxias and spastic paraplegias. EOCA, Early onset cerebellar ataxia with retained tendon reflexes
Sweden [10] Western Norway [11]a Benghazi (Libya) [12] Turin (Italy) [1] Zealand (Denmark) [13]b Cantabria (Spain) [7] Present study
1.2 1.0 0.4 1.0 0.8 4.7 2.1
1.0 0.5 2.3 1.5
0 0 1.2
11.9 2.1 c 1.3c 0.5 9.6 2.7
2.0 22.1 4.8 6.1 5.8 20.2 7.5
a Prevalence ratios were corrected by estimation of ascertainment probability. The actual number of cases was 5 for Friedreich's disease (FD), 31 for hereditary spastic paraplegia (HSP) and 68 for all hereditary ataxias (HA) and HSP in a population of 725,000 inhabitants b Prevalence rates were estimated as the product of incidence density and duration of disease in a 10- to 50-year-old population. The actual number of cases was 10 for FD, 22 HSP and 59 for all HA and HSP in a population of 1,179,000 inhabitants ° Sporadic cases of spastic paraplegia were also included
only e x a m i n e d records f r o m hospitals and rehabilitation centres but interviewed general pratictioners and specialists w h o were likely to have patients with H A and H S P . In Italy free medical care and g o v e r n m e n t financial assistance for the disabled bring patients to medical attention. Table 2 summarizes the m o s t relevant prevalence studies on H A and H S P . Most of t h e m give prevalence ratios close to ours. H i g h e r prevalence values were rep o r t e d in two studies [7, 11]. Skre [11] d o u b l e d his actual value, correcting it by ascertainment probability. T h e high prevalence ratio f o u n d by Polo et al. [7] might be due, in recessive forms, to the general p o p u l a t i o n ' s high consanguinity and, in d o m i n a n t forms, to the large n u m ber o f s e c o n d a r y cases. T h e prevalence ratio w h e n only index cases were considered was 9.4 × 10 -5. A lower prevalence ratio was f o u n d by SjOgren [10], but the aut h o r himself considered his estimate to be 50% of the actual ratio. O u r prevalence ratio for F D is slightly higher than m o s t values r e p o r t e d in the literature and lower than that f o u n d by Polo et al. [7]. A prevalence ratio of 1.2 x 10 .5 was recently f o u n d in n o r t h - w e s t e r n Italy [6]. G i v e n a disease d u r a t i o n of 30 years and a n o r m a l life expectancy of 70 years, we can estimate f r o m o u r prevalence ratio a birth incidence of 4.9 x 10 .5 (2.1 × 10 .5 x 70/30) [14]. This value is very close to the 4.5 × 10 .5 estimated f r o m the f r e q u e n c y o f first-cousin marriages in Italy [8] and higher than the 2.8 × 10 .5 f o u n d during the period 1948-1964 in n o r t h - w e s t e r n Italy [6]. T h e E O C A prevalence ratio in Molise is intermediate a m o n g r e p o r t e d values. A s far as A T is c o n c e r n e d , s o m e surveys [7, 12] r e p o r t e d no case and others [1, 10, 11, 13] gave no figures. Sedgwick and B o d e r [9] r e p o r t e d a pre-
valence of 1.5 × 10 .5 in the 5- to 18-year-old p o p u l a t i o n of Los Angeles. H S P prevalence ratios higher than ours have b e e n r e p o r t e d by Skre [11], w h o corrected his data by ascertainment probability, and by Polo et al. [7]. In this last survey only 9 patients were p r o b a n d s , whereas the o t h e r 40 were s e c o n d a r y cases. D o m i n a n t H S P families o u t n u m b e r the recessive in some studies [7, 11], while the reverse o c c u r r e d in the L i b y a n study [12] and ours.
In conclusion, F D is the m o s t f r e q u e n t f o r m of H A in Molise, accounting for 44% of cases; E O C A and A T follow in that order; no d o m i n a n t f o r m of H A was found; in H S P also there was a p r e p o n d e r a n c e of recessive cases.
Acknowledgement. This work was supported by grants from CNR (no. 89.0327) and the Italian Ministry of Health.
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