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A 13-year follow-up of Finnish patients with Salla disease.

Paavola LE, Remes AM, Harila MJ, Varho TT, Korhonen TT, Majamaa K - J Neurodev Disord (2015)

Bottom Line: Verbal comprehension skills did not diminish during the follow-up, but productive speech deteriorated because of dyspraxia and dysarthria.Thus, the results indicate better prognosis in cognitive skills than earlier assumed.The early neurocognitive development predicts the later course of motor and cognitive development.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Oulu University Hospital, P.O. Box 20, 90029 Oulu, Finland ; Department of Clinical Medicine, Neurology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland ; Department of Clinical Neurology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland ; Neural Ltd, Center of Neuropsychology, Isokatu 16 B 18, 90100 Oulu, Finland.

ABSTRACT

Background: Salla disease (SD) is a rare lysosomal storage disorder leading to severe intellectual disability. SD belongs to the Finnish disease heritage, and it is caused by mutations in the SLC17A5 gene. The aim of the study was to investigate the course of neurocognitive features of SD patients in a long-term follow-up.

Methods: Neuropsychological and neurological investigations were carried out on 24 SD patients, aged 16-65 years, 13 years after a similar examination.

Results: The survival analysis showed excess mortality among patients with SD after the age of 30 years. The course of the disease was progressive, but follow-up of SD patients revealed that motor skills improved till the age of 20 years, while mental abilities improved in most patients till 40 years of age. Verbal comprehension skills did not diminish during the follow-up, but productive speech deteriorated because of dyspraxia and dysarthria. Motor deficits were marked. Ataxia was prominent in childhood, but it was replaced by athetotic movements during the teens. Spasticity became more obvious with age especially in severely disabled SD patients.

Conclusions: Younger SD patients performed better in almost every task measuring mental abilities that then seem to remain fairly constant till early sixties. Thus, the results indicate better prognosis in cognitive skills than earlier assumed. There is an apparent decline in motor skills after the age of 20 years. The early neurocognitive development predicts the later course of motor and cognitive development.

No MeSH data available.


Related in: MedlinePlus

Survival of 41 subjects with SD. Kaplan-Meier survival analysis and log-rank statistics were used to compare the age at death (dotted line) and matched life expectancy at birth (solid line). Log-rank analysis of the significance of the difference, p = 0.00005
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Fig1: Survival of 41 subjects with SD. Kaplan-Meier survival analysis and log-rank statistics were used to compare the age at death (dotted line) and matched life expectancy at birth (solid line). Log-rank analysis of the significance of the difference, p = 0.00005

Mentions: The 41 patients with SD who had participated in the baseline study were included in a survival analysis. The analysis showed excess mortality among patients with SD after the age of 30 years (Fig. 1). No difference was noted between the genders (mean survival 57.2 years for women, 59.0 years for men; p = 0.88, log-rank analysis). Interestingly, four out of the eight deceased persons had died at the age of 27 years (range, 20–40 years) younger than expected, while four subjects had died 7 years (range, −1–9 years) older than expected. There are no previous studies on mortality of SD patients, and hence, it is not known whether such subgroups are true. Anyhow, these two groups did not differ with respect to mental developmental age (p = 0.69, Mann–Whitney U test) or motor developmental age (p = 0.89) at the baseline visit. All the eight deceased persons had epilepsy during life, but unfortunately, we could not find out whether epilepsy was the cause of death. Patients with SD live longer than those with aspartylglucosaminuria (AGU), another lysosomal storage disorder belonging to the Finnish disease heritage. On average, women with AGU live to 40 years and men to 35 years [26].Fig. 1


A 13-year follow-up of Finnish patients with Salla disease.

Paavola LE, Remes AM, Harila MJ, Varho TT, Korhonen TT, Majamaa K - J Neurodev Disord (2015)

Survival of 41 subjects with SD. Kaplan-Meier survival analysis and log-rank statistics were used to compare the age at death (dotted line) and matched life expectancy at birth (solid line). Log-rank analysis of the significance of the difference, p = 0.00005
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4499899&req=5

Fig1: Survival of 41 subjects with SD. Kaplan-Meier survival analysis and log-rank statistics were used to compare the age at death (dotted line) and matched life expectancy at birth (solid line). Log-rank analysis of the significance of the difference, p = 0.00005
Mentions: The 41 patients with SD who had participated in the baseline study were included in a survival analysis. The analysis showed excess mortality among patients with SD after the age of 30 years (Fig. 1). No difference was noted between the genders (mean survival 57.2 years for women, 59.0 years for men; p = 0.88, log-rank analysis). Interestingly, four out of the eight deceased persons had died at the age of 27 years (range, 20–40 years) younger than expected, while four subjects had died 7 years (range, −1–9 years) older than expected. There are no previous studies on mortality of SD patients, and hence, it is not known whether such subgroups are true. Anyhow, these two groups did not differ with respect to mental developmental age (p = 0.69, Mann–Whitney U test) or motor developmental age (p = 0.89) at the baseline visit. All the eight deceased persons had epilepsy during life, but unfortunately, we could not find out whether epilepsy was the cause of death. Patients with SD live longer than those with aspartylglucosaminuria (AGU), another lysosomal storage disorder belonging to the Finnish disease heritage. On average, women with AGU live to 40 years and men to 35 years [26].Fig. 1

Bottom Line: Verbal comprehension skills did not diminish during the follow-up, but productive speech deteriorated because of dyspraxia and dysarthria.Thus, the results indicate better prognosis in cognitive skills than earlier assumed.The early neurocognitive development predicts the later course of motor and cognitive development.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Oulu University Hospital, P.O. Box 20, 90029 Oulu, Finland ; Department of Clinical Medicine, Neurology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland ; Department of Clinical Neurology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland ; Neural Ltd, Center of Neuropsychology, Isokatu 16 B 18, 90100 Oulu, Finland.

ABSTRACT

Background: Salla disease (SD) is a rare lysosomal storage disorder leading to severe intellectual disability. SD belongs to the Finnish disease heritage, and it is caused by mutations in the SLC17A5 gene. The aim of the study was to investigate the course of neurocognitive features of SD patients in a long-term follow-up.

Methods: Neuropsychological and neurological investigations were carried out on 24 SD patients, aged 16-65 years, 13 years after a similar examination.

Results: The survival analysis showed excess mortality among patients with SD after the age of 30 years. The course of the disease was progressive, but follow-up of SD patients revealed that motor skills improved till the age of 20 years, while mental abilities improved in most patients till 40 years of age. Verbal comprehension skills did not diminish during the follow-up, but productive speech deteriorated because of dyspraxia and dysarthria. Motor deficits were marked. Ataxia was prominent in childhood, but it was replaced by athetotic movements during the teens. Spasticity became more obvious with age especially in severely disabled SD patients.

Conclusions: Younger SD patients performed better in almost every task measuring mental abilities that then seem to remain fairly constant till early sixties. Thus, the results indicate better prognosis in cognitive skills than earlier assumed. There is an apparent decline in motor skills after the age of 20 years. The early neurocognitive development predicts the later course of motor and cognitive development.

No MeSH data available.


Related in: MedlinePlus