Infantile type of so-called neuronal ceroid-lipofuscinosis

Journal of the neurological Sciences, 18 ( 1973) 257-267 © Elsevier Scientific Publishing Company, Amsterdam

257 Printed in The Netherlands

Infantile Type of so-called Neuronal Ceroid-Lipofuscinosis P a r t 1. A Clinical S t u d y o f 15 P a t i e n t s

P. SANTAVUORI, M. HALTIA, J. RAPOLA AND CHRISTINA RAITTA The Children's Hospital, 2nd Department of Pathology, and Department of Ophthalmology, University of Helsinki, Helsinki (Finland) (Received 18 August, 1972)

INTRODUCTION

On the basis of 3 personal observations and of a report by J~insk# (1908), Bielschowsky (1913) delineated a late infantile form Of amaurotic family idiocy as a variant of the juvenile form of the disease, previously described by Batten (1903), Spielmeyer (1905) and Vogt (1905). Since then a limited number of similar cases have been reported, recently extensively reviewed by Zeman, Donahue, Dyken and Green (1970). Because of the nature of the pathological changes, Zeman et al. (1970) included these cases in the group of so-called neuronal ceroid-lipofuscinoses (NCL) (Zeman and Dyken 1969) or Batten's disease as the late infantile or Jfinsk3)-Bielschowsky subtype. They also emphasized the distinction between the J~nsk~,-Bielschowsky type of NCL and various types of gangliosidosis of late infantile onset, viz. GMx-gangliosidosis (types I and II) and the late infantile form of GM2-gangliosidosis, since no specific abnormalities in ganglioside metabolism have been detected in NCL patients. According to most authors (Bielschowsky 1913 ; Zeman et al. 1970; Menkes, Andrews and Cancilla 1971) typical late infantile cases of NCL have their clinical onset at 2 to 5 years of age with seizures. The course of the disease is characterized by psychomotor deterioration and severe convulsions, but visual symptoms are said to be late and unimportant. We have recently observed a series of 15 patients whose disease seems to be close to the NCL group but which showed many exceptional features. The disease had its clinical onset during the second year of life or even earlier. It was characterized by a very rapid course with early and important ophthalmological findings and relative paucity or even absence of convulsions. The diagnostic histological and ultrastructural features*, reported in Part 2 of this investigation (Haltia, Rapola, Santavuori and Ker~inen 1973), were uniform and differed from most previous observations on late infantile amaurotic idiocy. This work was supported by the National Research Council for Medical Sciences and the Emil Aaltonen Foundation, Finland. Consent for the brain biopsies was obtained after complete and detailed information was given to the parents.

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P. S A N T A V U O R I , M. H A L T I A , J. R A P O L A , C. R A I T T A

CLINICAL FINDINGS

The present series is composed of 15 patients, 10 males and 5 females from 13 families. The case histories, physical findings and results of special investigations in these patients were so uniform (see Table 1) that only 2 illustrative case reports are presented in detail. TABLE 1 AGE OF ONSET (MONTHS) OF PRINCIPAL SYMPTOMS AND SIGNS

Case number Sex

1 F

2 M

3 M

4 F

5a M

6 F

7a M

8~ F

9 M

l0 a M

11 M

12 M

13 M

t4 M

15 F

Suspicion of mental retardation

14

15

17

8

16

16

11

15

14

14

18

14

18

12

12

Hypotonia

15

12

12

8

20

18

12

12

17

?

21

16

16

12

12

Ataxia

15

15

17

9

-

18

12

12

17

21

17

'?

14

?

19

Pronounced mental retardation

16

22

19

14

22

20

16

17

20

21

21

19

20

18

19

Visual failure

22

23

16

21

16

17

12 15 21 21

22

19 20 24 24

Myoclonic jerks

18

24

24

22

21

23

21 21 21

21

16 20 23 19

"Knitting" hyperkinesia

18

23

23

24

22

23

23 23 21

Convulsions

16

29

24

27

--

-

27

24

-

Burnt-out stage

24

29

25

23

34

24

24

24

24

?

Present age (years)

3.9

3.6

2.8

3.2

5.1

2.7

3.3

2.3

2.2

5A b

a C a s e s 5 and 10

?

21 -

21

- -19

-

34

19

6.8 b

18 23

28

24

23

28

3.0 3.5

4.0

7.1

as well as 7 and 8 were siblings.

Age at death.

Inheritance In 2 of the 13 families 2 children were affected (Cases 7 and 8 and 5 and 10). The parents, their siblings, and grandparents were not affected. Both boys and girls were affected. This indicates an autosomal recessive m o d e of inheritance.

Clinical course and physical findings For all patients gestation and delivery were uneventful except in 1 patient (Case 1 l) who was born by caesarean section. Birth weight varied between 2700 and 3900 g. The neonatal period was uneventful except in 1 patient (Case 3) who had had transitory hypocalcemia. In all patients the developmental milestones were normal until the age of 8 months. Except for 2 patients (Cases 2 and 4) all patients learned to speak single words. Eight children learned to walk. In most patients retardation of mental development was noted at the age of 1-1½ years, in 2 patients even earlier. Slightly later, m o t o r development ceasedl Thereafter generalized hypotonia and truncal and limb ataxia appeared. In some cases hypotonia

INFANTILE TYPE OF SO-CALLED NEURONAL CEROID-LIPOFUSCINOSIS, PART 1

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and ataxia were the initial signs. In many patients (Cases 1, 3, 6, 9, 11 and 13) the ataxia was very severe and led rapidly to severe motor disability. Tendon reflexes were exaggerated in all patients at a relatively early stage and this was later accompanied by clonus. All patients had definite microcephaly which became more pronounced with increasing age and was more marked when the disease began during the first year. In all patients the head circumference was 2 SD. below the mean for Finnish children of comparable age (Kantero and Tiisala 1971) (Fig. 1). cm

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of head circumferencefor normal Finnish boys(Kantero and Tiisala 1971).At birth the head circumferences were within the normal range but later fell 2 SD or more below the mean in every case (three recordings were available in Cases 2, 3, and 5). Visual disturbances were already observed at the age of 12 months. In all patients visual impairment was established at ophthalmological examination after the age of 18 months. All patients had myoclonic jerks at about 2 years of age. They were first observed in the limbs and in most cases they increased continuously in severity and occurred also in the face and trunk. At about the same time characteristic "knitting" movements were observed in the hands and forearms which disappeared again after a few months. Not all patients developed convulsions during the follow-up period. Three (Cases 1, 2 and 11) had both myoclonic astatic and partial generalized convulsions. In all patients the disease reached a burnt-out stage during the third year. They were completely unresponsive and without voluntary movements. The patients were hypotonic but had episodes of opisthotonus with hypertonic flexion in the arms and extension in the legs, and in some cases also with rigidity. There was no head control. Later most of the children were extremely hyperexcitable and any kind of stimulation increased the myoclonic jerks. At the terminal stage, so far observed only in Cases 10, 11 and 15, the patients had a permanently increased flexor tonus in all limbs. Two of

260

P. SANTAVUORI, M. HALTIA, J. RAPOLA, C. RAITTA

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INFANTILE TYPE OF SO-CALLED NEURONAL CEROID-LIPOFUSCINOSIS, PART l

261

the children (Cases 10 and 11) died at the ages of 5 years 10 months and 6 years 10 months, respectively, of a respiratory infection.

Special investigations 12 of the 15 patients were examined by an ophthalmologist. The ophthalmological findings were uniform (see Table 2). Except for Case 1, all patients showed signs of severe visual failure at the first examination. The ophthalmoscopic findings were hypopigmentation of the fundus and optic atrophy and retinal dystrophy with brownish discoloration of the macula. There was no pigment aggregation in the peripheral retina nor accumulation of pigment in the macular area. The electroretinogram was abolished. None of the patients had a normal electroencephalogram (EEG). The most characteristic features were slowing of the rhythmic activity and later, usually after some months, diminution in overall amplitude, which in some cases was first seen over the parietal and occipital regions (Fig. 2). In 2 patients (Cases 8 and 10) the EEG was registered only during sleep. Five patients had sharp waves and spikes in the frontal, central and temporal regions, sometimes only seen during sleep. There was no focal

Case N 1 14yrs

Cose N 2 1.9 y r s

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C a s e N 12 2 9 y r s

Fig. 2. Electroencephalographic records at various stages of the disease showing the slowing of the rhythmic activity and diminution in amplitude seen at first over the posterior regions.

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P. SANTAVUOR1, M. HALTIA, J. RAPOLA, C. RAITTA

abnormality. In 3 patients (Cases 1, 4 and 11) in whom the first EEG was taken before the age of 18 months, there were scattered high amplitude delta waves and spike-andwave complexes in different regions. There were also many generalized irregular bursts of sharp and slow waves and spike-and-wave discharges. There was no driving at photic stimulation. After some months the rhythmic activity decreased in amplitude and disappeared first over the posterior regions. In all patients who were followed to an age of more than 3 years (Cases 1, 2, 5, 11, 12, 13, 14 and 15) serial records showed a largely or completely isoelectric EEG. The results of electromyographic (EMG) and nerve conduction velocity studies made in 7 patients (Cases 1, 2, 3, 4, 5, 9 and 13) were within normal limits. Pneumoencephalography was performed in all patients, except 1 (Case 8). Nine patients had severe generalized supra- and infratentorial atrophy. In 3 patients (Cases 3, 4 and 9) the atrophy was less pronounced and involved mainly the third ventricle and cisterna pontis and interpeduncularis. Two children (Cases 5 and 11) had only slight dilatation of the ventricles. Routine blood and urinary tests were normal in all patients. No vacuolated lymphocytes were found in the peripheral blood. In 9 patients hypergranulation of the neutrophils was specially investigated but was found only in 5 patients. Both parents of 2 patients and the mothers of 2 more were also investigated but they did not reveal any neutrophilic hypergranulation or vacuolated lymphocytes. Bone marrow (Cases 2, 5 and 7) showed no abnormality. Serum lactic acid dehydrogenase was high in 3 patients. Serum transaminase and alkaline phosphatase activity as well as serum calcium levels were normal. There was 1 patient (Case 13) with high acid phosphatase activity. Serum pyruvate and lactic acid levels were within normal limits in 2 patients. A urinary amino acid thin-layer chromatogram revealed a non-specific generalized aminoaciduria in 1 patient (Case 7); all others had a normal urinary amino acid chromatogram (in Case 10 no analysis was made). Urinary arylsulphatase activity was investigated in 7 patients and was within normal limits. The CSF cell count as well as the protein concentration and electrophoretic pattern were normal in every patient (in Case l0 no electrophoresis was done). ILLUSTRATIVE CASE REPORTS Case 2

This boy is the second child of healthy non-related parents. There is no family history of mental retardation. Pregnancy and delivery were without complication. The boy was born 3 weeks before term and his birth weight was 3800 g, Apgar-score 10. The neonatal period was uneventful. The developmental landmarks were normal up to the age of 8 months. He rolled over at the age of 5 months, grasped objects at the age of 4 months, but could not sit without support before the age of 12 months. He crawled at the age of 12 months and stood up with support at the age of 15 months but never learned to walk. At the age of about 12 months he could speak single words but after the age of 18 months his speech gradually deteriorated to unintelligible syllables and at the same time his motor development seemed to cease and then to regress. At the age of 10 months the patient was seen for the first time at the outpatient department of the University of Helsinki Children's Hospital, because of suspected microeephaly. His head circumference (43 cm) was below the 2.5th percentile. His weight was close to the 50th percentile, and his height'close to the 975th percentile. He had a divergent squint. When next seen at the age of 22 months his psychomotor development was markedly retarded. There was generalized hypotouia with truncal and limb ataxia. Tendon reflexes were normak X-ray examination of the skull showed microcephaly and closure of the sagittal suture, but no intracrauial ealeifieatious were observed.

INFANTILE TYPE OF SO-CALLED NEURONAL CEROID-LIPOFUSCINOSIS, PART

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He was admitted to the ward at the age of 23 months. He was severely retarded, had no speech or grasping ability, could not sit and had pronounced ataxia. Characteristic rotatory movements resembling knitting were observed in the forearms. His liver and spleen were not enlarged. His vision was impaired. The optic discs were pale and there was a greyish discoloration of the macula. Audiological examination revealed neural hearing loss. Pneumoencephalography disclosed a marked supra- and infratentorial atrophy. The EEG was abnormal with low voltage irregular 2.5~ cycles/sec delta-theta activity and single 1.5-3 cycles/ sec delta waves reaching 130/tV over the central and temporal regions, without lateralization. There was no response to photic stimulation. During sleep sharp waves were observed over the temporal regions. Motor conduction velocities in peripheral nerves were within normal limits. At the age of 29 months the boy was spastic with exaggerated tendon reflexes. Myoclonic jerks were observed in the limbs and trunk as well as nodding of the head. His head circumference was 45.5 cm. The optic discs were atrophic, the lustre of the retina around the macula was increased and the maculae were greyishbrown. The electroretinogram was abolished. There was no normal activity in the EEG. Low voltage 2.5-5 cycles/sec delta theta activity dominated in the anterior regions. In the posterior regions no activity could be registered. During sleep sharp waves were observed in the temporal and occipital regions. Because of the suspicion of focal fits therapy with phenobarbital 30 mg daily was begun. At the age of 30 months he was transferred to an Institute for the mentally retarded. He was unresponsive and without voluntary movements. He was lying in slight opisthotonus with increased flexor tonus in the upper limbs and hypertonic extension in the legs. Myoclonic jerks were frequent. As well as myoclonic jerks and myoclonic status the boy also had generalized convulsions. Laboratory examinations: Routine blood and urinary tests were normal. No vacuolated lymphocytes were revealed in peripheral blood, but there was abnormal hypergranulation of the neutrophils. Bone marrow did not show any abnormality. Serum lactic acid dehydrogenase, transaminase and alkaline phosphatase activity as well as serological tests for toxoplasmosis and rubeola were within normal limits. Urinary arylsulphatase excretion, and urinary amino acid thin-layer chromatograms were normal. The cerebrospinal fluid (CSF) cell count as well as the protein concentration (32 mg per 100 ml) and electrophoretic pattern were normal. Biopsies : No abnormality was detected in a sural nerve biopsy. A right frontal brain biopsy was performed at the age of 29 months and the specimen showed marked neuronal loss, characteristic accumulation of lipofuscin-like material in the remaining nerve cells and numerous macrophages in the cerebral cortex. Thin-layer chromatography did not show any specific abnormality in the ganglioside pattern.

Case 5 This boy is the fourth son of healthy non-related parents. The second child of the family (Case 10) died at the age of 5 years 10 months after a progressive neurological disease closely resembling that of the patient described here (see Appendix). Pregnancy and delivery were uneventful. The patient was born 18 days before term. His birth weight was 2840 g. He had no abnormalities during the neonatal period. He could sit without support at the age of 7 months and crawl at the age of 10 months, but could only stand up and walk with support at the age of 16 months. At the age of 12 months he could speak single words. At the age of 16 months his psychomotor development stopped and his vision was clearly impaired. At the age of 21 months he was admitted to a local hospital. He appeared to be mentally retarded but could still speak single words. He still crawled and was able to sit but could not stand or walk. He was generally hypotonic and had a few myoclonic jerks. The optic discs were somewhat pale and the macula was said to be red and oedematous. Pneumoencephalography revealed mild central atrophy. At the age of 22 months the boy was admitted to the University of Helsinki Children's Hospital. The patient was microcephalic with a head circumference of 48 cm and was severely retarded. He could no longer speak. He was hyperexcitable with characteristic knitting hyperkinesia of the upper limbs. There was hypotonia of the trunk, upper limbs and neck with extreme head lag, contrasted with the occasional high extensor tone of the lower limbs. His tendon jerks were brisk but no ankle clonus was elicited. He was blind. Ophthalmoscopic examination revealed optic atrophy, brownish discoloration in the macular areas and dystrophy of the peripheral retina. The electroretinogram was abolished. The EEG was markedly abnormal. Low voltage irregular 1.5 3 counts/sec delta-theta activity dominated. There was only some 4-6 counts/sec theta activity. Photic stimulation gave no response. The condition of the patient deteriorated steadily and at the age of 2 years 10 months all active movement was lost. At the age of 4 years the child was again seen at the Children's Hospital. In the supine position the upper limbs were flexed and the lower limbs had strong extensor tonus. All tendon jerks were extremely brisk, with clonus. The Babinski sign was positive on the left side. The EEG was isoelectric. Laboratory findings: Routine blood and urinary tests were normal. Neither vacuolated lymphocytes nor hypergranulation of the neutrophils were observed in peripheral blood. Bone marrow did not show any abnormality. Serum cholesterol, transaminase, calcium and alkaline phosphatase activity were normal.

264

P. SANTAVUORI, M. HALTIA, J. RAPOLA, C. RAITTA

Urinary arylsulphatase excretion and urinary amino acid thin-layer chromatogram were also normal. "lhc CSF cell count as well as the protein concentration (20 rag/100 ml) and electrophoretic pattern were within normal limits. Biopsies: Sural nerve biopsy disclosed no abnormality. A right frontal brain biopsy was performed at the age of 4 years and the specimen showed subtotal neuronal loss, storage o f a lipofuscin-like material in the few remaining nerve cells and numerous macropbages in the cerebral cortex. Appendix to case report 5: The second child of the family (case 10) developed normally until the age of 10 months. At the age of 21 months the child was admitted to the University of Helsinki Childrens' Hospital. He was clearly retarded, had microcepbaly (46.6 cm) and a convergent squint. His vision was impaired, tte had ataxia in the sitting position and could no longer stand. The EEG was abnormal and pneumoencephalogram showed marked brain atrophy. Deterioration was rapid and the boy died at the age of 5 years 10 months in a local hospital. No autopsy was performed.

DISCUSSION

The clinical picture of our patients with onset before the age of 18 months of rapid psychomotor deterioration combined with ataxia, frequent myoclonic jerks, visual failure and microcephaly is very characteristic. The early extinction of the electroretinogram, EEG records rapidly approaching isoelectricity, and normal CSF findings are additional characteristics which help to distinguish the present condition from most other progressive encephalopathies of the age group in question, including the gangliosidoses and leukodystrophies (Hagberg). Morphological findings are diagnostic and, supported by biochemical observations, show that our cases had some features in common with the group of NCL as defined by Zeman and Dyken (1969). However, from the clinical point of view our cases are easily differentiated from the classical Spielmeyer-Sj6gren type of NCL. Not only the early onset but also the fulminant course, early and pronounced ataxia, and severe myoclonus are inconsistent with the Spielmeyer-Sj6gren type. The occurrence of vacuolated lymphocytes in the peripheral blood of patients with the Spielmeyer-Sj6gren type of NCL was first observed in Finnish patients (Bagh and Hortling 1948), and has since been found as a constant phenomenon in this type of disease in Scandinavia (Plum and Stubbe-Tegelbjaerg 1961; Rayner 1962) although not in other countries (Zeman and Strouth 1967). In our patients vacuolated lymphocytes were never observed. Our series also displays a number of features which differ from those considered characteristic for the Jfinsk~-Bielschowsky type of NCL. The clinical symptoms of all of our 15 patients appeared before the age of 18 months, in some cases already during the first year. Microcephaly was noticed in most cases at the first examination, and in 1 patient (Case 2)as the first sign at 10 months of age, which suggests an even earlier onset of the disease process. At the age of 2 years, ~ patients had already reached the burnt-out stage. The time of onset in our patients is thus clearly different from that in the Jfinsk2~-Bielschowsky type of NCL which is usually said to begin at 2 to 5 years of age with seizures. Convulsions are a dominant feature even during the later course of the J~insk2)Bielschowsky type of NCL, and Zeman and Dyken (1969) suggest that they may be responsible for the rapid deterioration of the patients. In none of our patients were convulsions seen as the first symptom and there are 5 patients who are still without seizures. Two of these are over 5 years of age, one being alive and the other already dead. The 4 patients still alive and without convulsions have been severely affected

INFANTILE TYPE OF SO-CALLED NEURONAL CERO1D-LIPOFUSCINOSIS, PART

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for periods ranging from several months to years. The convulsions in the other patients have usually been relatively infrequent and of short duration. Only 1 child of our series has had a convulsion lasting as long as half an hour. We feel therefore, that convulsions cannot explain the rapid course of the disease in our patients. The characteristic EEG features in our patients are the slowing and diminution of the rhythmic activity rapidly approaching isoelectricity, as well as the absence of reaction to photic stimulation at an early phase of the disease. Pampiglione and Lehovsk~ (1968) described peculiar polyphasic spikes seen during photic stimulation with a low rate of flickering in the EEG in a group of patients with amaurotic idiocy which had begun at 2 to 5 years of age. This phenomenon is considered to be typical for the Jfinsk2~-Bielschowsky type and is useful in the differential diagnosis (Lehovsk2~ 1971). We have observed similar changes in the EEG of 6 patients with the typical clinical and morphological picture of the Jfinsk2~-Bielschowsky type (Santavuori et al., unpublished observations). Such changes were never observed in the patients of the present series. The slowing of the rhythmic activity and the diminishing amplitude, leading rapidly to an isoelectric EEG, are quite striking, as well as the fact that the children can still be alive several years after registration of an isoelectric EEG. Similar observations have been made in 1 case of NCL (Zeman et al. 1970) and in children with neonatal herpes simplex infection (Pettay, Leinikki, Donner and Lapinleimu 1972). The EEG findings probably reflect the rapidly progressive destruction of the cerebral cortex observed in our patients. All of our patients had markedly impaired vision or were blind and had funduscopic changes already at the age of 2 years. In all patients the electroretinogram was abolished, even where fundoscopic changes were relatively slight, as in 1 patient at 1 year 7 months (Case 3). These findings are unlike the findings in the Jfinsk2~-Bielschowsky type of NCL where the ophthalmological changes are considered to be late and unimportant (Zeman et al. 1970; Menkes et al. 1971 ; Copenhaver and Goodman 1960). Pigmentary degeneration of the macula has been described in many cases of the Jfinsk2~Bielschowsky type (Zeman et al. 1970). The macular dystrophy in our series, however, was distinctly different. Except for some slight brownish discoloration of the maculae, generalized hypopigmentation of the entire fundus was the rule, and no pigment aggregation of retinitis pigmentosa type could be seen. A survey of the literature has revealed some cases which bear a rather close resemblance to our patients. In the case of Richter and Parmelee (1935) the initial development of the patient was normal until 14 months of age, but after this the psychomotor condition of the patient deteriorated. There were no convulsions. At the age of 5 years he was in a state of decerebrate rigidity and remained so until his death 9 months later. The patient was blind and there was constant twitching of the arms and hands. The histological changes were very similar to the findings in our cases, as were those in the case of Tingey, Norman, Urich and Beasley (1958). By the age of 2 years a serious arrest of development of their patient had occurred and the girl was considered microcephalic. At that time she was not thought to be blind and no ophthalmoscopic examination was made. At no time did she have any fits. She died at the age of 4 years and 8 months. In the case of Hagberg, Sourander and Svennerholm (1968) the development of the

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patient stopped at the age of I year and then regressed. The child developed ataxia, her vision seemed to be impaired, and at the age of 2 years she was severely retarded. The EEG showed gravely depressed cerebral activity at the age of 23 years, and the child died at the age of 5 years i0 months. For a limited period she had nodding spells but no other types of convulsion. All this agrees with our cases, as do the histological alterations. The neuroretina had lost almost all of its ganglion cells and photoreceptor cells. However, the fundi were still said to be normal at the age of 23 years. Unfortunately, no electroretinography was performed. Somewhat similar cases were also reported by Levine, Lemieux, Brunning, White, Sharp, Harvey, Standlan and Krivit (1968) and by Ryan, Anderson, Menkes and Dennett (1970) although in their cases no ophthalmological changes were observed and retinal histology was apparently not examined. Zeman and Dyken (1969) mention among 26 cases of NCL 3 children with a clinical onset before 2 years of age but they do not give sufficient details to allow a comparison with our series. Although histological studies have shown that our series of 15 uniform cases, as well as the cases collected from the literature mentioned above and published under various designations, have a number of features in common with the group of NCL, our series does not conform to any of the previously recognized clinical types within this group. In our present state of ignorance of the basic biochemical defect or defects in NCL, it is not possible to decide whether these cases of early onset constitute a separate nosological entity or merely an unusual clinical variant of Batten's disease. However, from the practical point of view it is important to realize the existence of such cases of early NCL as, at least in Finland, the present condition appears to be by far the most common progressive encephalopathy in children under 2 years of age. The highest known prevalence (3.8/100000) for the classic juvenile SpielmeyerSj6gren type of NCL was recorded in Sweden (Sj6gren 1931). In this context it may be of interest to note that the Spielmeyer-Sj6gren type of NC L is also relatively common in Finland, its actual prevalence (3.2/100000) being even higher than the latest estimate for Sweden (Rayner 1962). Genetic studies are now in progress to determine whether the relatively frequent occurrence of the Spielmeyer-Sj6gren type and of the present condition together in the same area is a mere coincidence.

SUMMARY

A clinical description is given of a uniform series of 15 patients with a progressive encephalopathy. The disease had its clinical onset at the age of 8 to 18 months with rapid psychomotor deterioration, ataxia, and muscular hypotonia. Microcephaly and myoclonic jerks were other prominent features ; convulsions were few or did not occur at all. All patients were amaurotic by the age of 2 years and had optic atrophy and macular and retinal dystrophy without pigment aggregation. Early extinction of the electroretinogram and EEG records rapidly approaching isoelectricity were additional features. The clinical picture does not fit with any previously recognized type of amaurotic idiocy. However, the diagnostic morphological and biochemical findings (see Haltia et al. 1973) have a number of features in common with the group of so-called neuronal

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ceroid-lipofuscinoses. The relationship of the present condition and of some previously reported similar cases to the various forms of neuronal ceroid-lipofuscinosis is discussed.

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