- Email: [email protected]
Swallowing dysfunction in patients with nephropathic cystinosis
Molecular Genetics and Metabolism 126 (2019) 413–415
Contents lists available at ScienceDirect
Molecular Genetics and Metabolism journal homepage: www.elsevier.com/locate/ymgme
Swallowing dysfunction in patients with nephropathic cystinosis a
b
c
c
A.E. van Rijssel , S. Knuijt , K. Veys , E.N. Levtchenko , M.C.H. Janssen a b c
a,⁎
T
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands Department of Pediatrics & Department of Growth and Regeneration, University Hospitals Leuven & University of Leuven, Leuven, Belgium
ARTICLE INFO
ABSTRACT
Keywords: Cystinosis Nephropathic Swallowing dysfunction Dysphagia?
Introduction: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. The aim of this study was to explore the swallowing function in patients with cystinosis by use of the Test of Mastication and Swallowing Solids (TOMASS), and to compare their performance with patients with myotonic dystrophy type 1 – a neuromuscular disease in which dysphagia for solid food is a known problem. Methods: Twenty adult patients with cystinosis (11 men and 9 women, range 19–51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 20–60 years) were included. All cystinosis patients were treated with cysteamine. Data of the two groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. Results: There was a significant difference in the number of bites, masticatory cycles, swallows and total time between the normal values and cystinosis patients. The results of the cystinosis patients were comparable to those of the patients with myotonic dystrophy. Discussion and conclusion: Adult patients with cystinosis have significant dysphagia for solid food. Clinicians treating these patients should be aware of this fact. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients in order to regularly follow-up swallowing function.
1. Introduction Nephropathic cystinosis is a rare autosomal recessive disease caused by mutations in the lysosomal cystine transporter cystinosin encoded by the CTNS gene. The disease is characterized by lysosomal cystine accumulation throughout the body. Most children present during the first year of life with generalized proximal tubular dysfunction (renal Fanconi syndrome). If left untreated, the disease progresses towards end-stage renal disease around the age of 10 years. The advent of renal replacement therapy and cysteamine allowed cystinosis patients to survive into adulthood. Cystinosis is treated by administration of the cystine-depleting agent cysteamine, which slows down the progression of renal failure and
prevents the development of extra-renal complications. Treatment with cysteamine should be initiated as early as possible and continued lifelong, even after kidney transplantation in order to protect extrarenal organs. Life expectancy of cystinosis patients has substantially improved and is now above 50 years [1]. Despite treatment with cysteamine numerous extrarenal manifestations of the disease occur, affecting eyes, endocrine organs, gastrointestinal tract, central and peripheral nervous systems and muscles. Dysphagia for solid food was mentioned previously in patients with cystinosis [2,3]. Both pharyngeal and oral dysfunction were observed and have been attributed to muscle dysfunction. In 2017, the Test of Mastication and Swallowing Solids (TOMASS,) was published and validated [4]. The aim of this study was to objectify
⁎ Corresponding author at: Department of Internal Medicine, Radboud University Medical Center, Huispost 463, Geert Grooteplein 10 6500 HB, Nijmegen PO BOX 9101, the Netherlands. E-mail address: [email protected] (M.C.H. Janssen).
https://doi.org/10.1016/j.ymgme.2019.01.011 Received 29 December 2018; Received in revised form 16 January 2019; Accepted 16 January 2019 Available online 22 January 2019 1096-7192/ © 2019 Elsevier Inc. All rights reserved.
Molecular Genetics and Metabolism 126 (2019) 413–415
A.E. van Rijssel et al.
Table 1 Characteristics of the cystinosis patients. Patient
Age (yr)
Sex (m/f)
Length (cm)
Weight (kg)
BMI (kg/m2)
Kidney transplantation (yes/no)
Daily cysteamine dose mg/kg
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
25 29 51 18 32 28 24 26 27 22 22 21 38 19 24 41 34 43 37 28
m m f m m m f f f m m m m m f f f f f m
163 169 155 176 176 178 155 161 150 150 170 171 158 184 159 150 140 151 147 168
57.4 69.4 50.2 59.6 68 54 46.8 58 44.6 49.4 55.6 57.6 62.3 75.4 53.6 36.2 53 59.4 67 68
21.6 24.3 20.8 19.4 21.9 17 19.5 22.4 20 21.8 19.2 19.7 24.9 22.2 21.2 16.1 27 25.5 31 24.1
yes yes yes no yes no yes yes yes no yes yes yes no yes yes yes yes yes yes
34.0 39.1 30.0 40.2 61.8 33.3 43.2 33.6 30.1 36.0 42.8 36.7 28.6 50.0 25.5 29.2 30.2 25.8 9 34.2
2.4. Statistical analysis
the problems of solid food ingestion in patients with cystinosis, using the TOMASS. We compared the results with normative data and a patient group in which dysphagia is a prominent symptom: myotonic dystrophy type 1 (MD1). MD1 is part of a group of inherited disorders called muscular dystrophies [5]. It is a multisystem disease, characterized by progressive myotonia (prolonged muscle contractions after use) and muscle weakness. In MD1, follow-up of dysphagia by a speechtherapist is usual care, while patients with cystinosis are hardly referred to speech-therapists [6].
We checked whether the variables were normally distributed using the Shapiro-Wilk test. In case of normally distributed variables, data of the two patient groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. The significance of both tests was set at p < .05. IBM SPSS statistics 22 software (IBM, Chicago) was used to perform the statistical analysis.
2. Methods
3. Results
2.1. Patients
3.1. Cystinosis patients
Twenty patients with nephropathic cystinosis (11 men and 9 women, range 19–51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 21–66 years) were included. Sex, age and body mass index were gathered as personal characteristics. All patients with cystinosis were treated with cysteamine. They reported no spontaneous complaints of dysphagia.
Table 1 shows the characteristics of the cystinosis patients. One patient was not able to perform the TOMASS. The variables ‘bites’, ‘swallows’ and ‘total time’ were not normally distributed. In Table 2, the TOMASS results of the cystinosis patients are compared to the healthy controls. It demonstrates that there is a significant difference in the number of bites (p < .01), masticatory cycles (t = −6.08, p < .01), swallows (p < .01) and total time (p < .01) between the normal values and healthy controls. The mean swallowing speed was 24.21 ml/s, which is normal. Looking at individual patients, only two patients (17 and 18) scored below 10 ml/s.
2.2. TOMASS Patients were asked to eat a standardized cracker (Albert Heijn Basic), ‘as quickly as is comfortably possible’. The number of bites, masticatory cycles, swallows per cracker and total time were registered. Before the start of the test, patients have to drink 150 ml water [4]. In our patients, this was achieved by examining the swallowing speed (see next paragraph). The normative data from 107 healthy adults between 20 and 70 years of age were derived from the Dutch database which was used for the development of the TOMASS [4].
Table 2 TOMASS results of the healthy adults, cystinosis patients and MD1 patients. The p-values indicate the difference between the patient group and healthy adults.
2.3. Swallowing speed To test the swallowing speed, a timed test of swallowing was used [7]. Patients have to drink 150 ml of water as quickly as possible, but they have to take care and stop if difficulties arise. The swallowing speed is supposed to be > 10 ml/s. Below 10 ml/s is an index of abnormal swallowing. 414
Healthy adults
Cystinosis
MD1
Mean (SD)
Mean (SD)
Mean (SD)
p-value
p-value
2.74 (1.20) p < .01 57.53 (28.11) p < .01 3.26 (1.59) p < .01 58.77 (28.89) p < .01
2.10 (0.99) p = .73 49.30 (15.69) p < .01 2.60 (0.84) p < .01 53.10 (15.85) p < .01
Bites (n)
1.97 (1.11)
Masticatory cycles (n)
34.39 (11.78)
Swallows (n)
1.65 (0.87)
Total time (sec)
28.53 (10.80)
Molecular Genetics and Metabolism 126 (2019) 413–415
A.E. van Rijssel et al.
3.2. Myotonic dystrophy
pharyngeal (pharyngeal pressure generation) stages of swallowing. Radiologic barium swallowing examination or videofluoroscopy is still seen as the gold standard for dysphagia assessment, but these examinations are more time consuming, more expansive and use radiation and contrast fluid. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients. We can regularly follow-up, even from relatively young ages, because the TOMASS is also validated in children [11]. If patients experience problems performing the TOMASS, referral to a speech therapist should be considered for education and awareness, to correct inadequate compensations and to learn to apply adequate compensations, like adjustments of food consistencies, consistently swallowing a bolus twice (double swallow) or drinking during or after a meal.
In MD1, the variable ‘total time’ was not normally distributed. In Table 2, the results of the patients with myotonic dystrophy are compared to the healthy controls. There is a significant difference in the number of masticatory cycles (t = −3.71), p < .01), swallows (t = −3.30, p < .01) and total time (p < .01) between the normal values and myotonic dystrophy patients. The was no significant difference between the two groups regarding the number of bites (t = −0.35, p = .73). 3.3. Cystinosis vs myotonic dystrophy Finally, we compared both patient groups. Only the variable ‘masticatory cycles’ was tested parametrically. There were no significant differences between the two patient groups regarding the number of bites (p = .18), masticatory cycles (t = 1.01, p = .32), swallows (p = .43) and total time (p = .84).
References
4. Discussion and conclusion
[1] E. Ivanova, M.G. de Leo, M.A. De Matteis, E. Levchenko, Cystinosis: clinical presentation, pathogenesis and treatment, Pediatr. Endocrinol. Rev. 12 (Suppl. 1) (2014) 176–184. [2] B.C. Sonies, E.F. Ekman, H.C. Andersson, et al., Swallowing dysfunction in nephropathic cystinosis, N. Engl. J. Med. 323 (1990) 565–570. [3] B.C. Sonies, P. Almajid, R. Kleta, et al., Swallowing dysfunction in 101 patients with nephropathic cystinosis, Medicine 147 (4) (2005) 242–250. [4] M.L. Huckabee, T. McINtosh, L. Fuller, et al., The test of masticating and swallowing solids (TOMASS): reliability, validity and international normative data, Int. J. Lang. Commun. Disord. 53 (1) (2018) 144–156. [5] G. Meola, R. Cardani, Myotonic dystrophies: an update on clinical aspects, genetic, pathology, and molecular pathomechanisms, Biochim. Biophys. Acta 1852 (2015) 594–606. [6] G.B. Langman, B.A. Barshop, G. Deschenes, et al., Controversies and research agenda in nephropathic cysstinosis: conclusions from a “Kidney Disease: improving global outcomes”(KDIGO) Controversies Conference, Kidney Int. 89 (2016) 1192–1203. [7] K.M. Nathadwarawala, J. Nicklin, Wiles Cm, A timed test of swallowing capacity for neurological patients, J. Neurol. Neurosurg. Psychiatry 55 (9) (1992) 822–825. [8] W.A. Gahl, G.F. Reed, J.G. Thoene, et al., Cysteamine therapy for children with nephropathic cystinosis, N. Engl. J. Med. 316 (1987) 971–977. [9] T.C. Markello, I.M. Bernardini, W.A. Gahl, Improved renal function in children with cystinosis treated with cysteamine, N. Engl. J. Med. 328 (1993) 1157–1162. [10] W.A. Gahl, J.Z. Balog, R. Kleta, Nephropathic cystinosis in adults: Natural history and effects of oral cysteamine therapy, Ann. Intern. Med. 147 (2007) 242–250. [11] U. Frank van de, L. Engel-Hoek, D. Nogueira, A. Schindler, S. Adams, M. Curry, M.L. Huckabee, International standardisation of the test of masticating and swallowing solids in children, J. Oral. Rehabil. 46 (2) (2019) 161–169.
Since patients with nephropathic cystinosis are currently treated with cysteamine, they have a better life expectancy [8,9]. When they become older, more extra–renal complications occur. One of these complications is swallowing dysfunction. In this study we demonstrated with a simple non-invasive test that cystinosis patients without clear complaints of dysphagia need more bites, more mastication cycles, more swallows and more time to eat a small cracker. In fact, they score equally to patients with MD1, in which dysphagia is a prominent symptom. In general, cystinosis patients have no difficulties in swallowing liquids. In cystinosis, one of the long-term major complications is myopathy, beginning with weakness and atrophy of the hand, extending to the upper extremities, the muscles involved swallowing, thoracic muscles and eventually the entire body's musculature. It was demonstrated that the frequency of myopathy is related to the duration of cysteamine therapy, but it is not known whether this represents a delay in onset of the myopathy or a complete prevention of it [10]. Clinicians taking care of patients with cystinosis should be aware of swallowing dysfunction in these patients. The TOMASS is the only noninvasive clinical tool to quantify solid food ingestion. It is supposed to identify especially problems in the oral (bolus preparation) and
415
Contents lists available at ScienceDirect
Molecular Genetics and Metabolism journal homepage: www.elsevier.com/locate/ymgme
Swallowing dysfunction in patients with nephropathic cystinosis a
b
c
c
A.E. van Rijssel , S. Knuijt , K. Veys , E.N. Levtchenko , M.C.H. Janssen a b c
a,⁎
T
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands Department of Pediatrics & Department of Growth and Regeneration, University Hospitals Leuven & University of Leuven, Leuven, Belgium
ARTICLE INFO
ABSTRACT
Keywords: Cystinosis Nephropathic Swallowing dysfunction Dysphagia?
Introduction: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. The aim of this study was to explore the swallowing function in patients with cystinosis by use of the Test of Mastication and Swallowing Solids (TOMASS), and to compare their performance with patients with myotonic dystrophy type 1 – a neuromuscular disease in which dysphagia for solid food is a known problem. Methods: Twenty adult patients with cystinosis (11 men and 9 women, range 19–51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 20–60 years) were included. All cystinosis patients were treated with cysteamine. Data of the two groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. Results: There was a significant difference in the number of bites, masticatory cycles, swallows and total time between the normal values and cystinosis patients. The results of the cystinosis patients were comparable to those of the patients with myotonic dystrophy. Discussion and conclusion: Adult patients with cystinosis have significant dysphagia for solid food. Clinicians treating these patients should be aware of this fact. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients in order to regularly follow-up swallowing function.
1. Introduction Nephropathic cystinosis is a rare autosomal recessive disease caused by mutations in the lysosomal cystine transporter cystinosin encoded by the CTNS gene. The disease is characterized by lysosomal cystine accumulation throughout the body. Most children present during the first year of life with generalized proximal tubular dysfunction (renal Fanconi syndrome). If left untreated, the disease progresses towards end-stage renal disease around the age of 10 years. The advent of renal replacement therapy and cysteamine allowed cystinosis patients to survive into adulthood. Cystinosis is treated by administration of the cystine-depleting agent cysteamine, which slows down the progression of renal failure and
prevents the development of extra-renal complications. Treatment with cysteamine should be initiated as early as possible and continued lifelong, even after kidney transplantation in order to protect extrarenal organs. Life expectancy of cystinosis patients has substantially improved and is now above 50 years [1]. Despite treatment with cysteamine numerous extrarenal manifestations of the disease occur, affecting eyes, endocrine organs, gastrointestinal tract, central and peripheral nervous systems and muscles. Dysphagia for solid food was mentioned previously in patients with cystinosis [2,3]. Both pharyngeal and oral dysfunction were observed and have been attributed to muscle dysfunction. In 2017, the Test of Mastication and Swallowing Solids (TOMASS,) was published and validated [4]. The aim of this study was to objectify
⁎ Corresponding author at: Department of Internal Medicine, Radboud University Medical Center, Huispost 463, Geert Grooteplein 10 6500 HB, Nijmegen PO BOX 9101, the Netherlands. E-mail address: [email protected] (M.C.H. Janssen).
https://doi.org/10.1016/j.ymgme.2019.01.011 Received 29 December 2018; Received in revised form 16 January 2019; Accepted 16 January 2019 Available online 22 January 2019 1096-7192/ © 2019 Elsevier Inc. All rights reserved.
Molecular Genetics and Metabolism 126 (2019) 413–415
A.E. van Rijssel et al.
Table 1 Characteristics of the cystinosis patients. Patient
Age (yr)
Sex (m/f)
Length (cm)
Weight (kg)
BMI (kg/m2)
Kidney transplantation (yes/no)
Daily cysteamine dose mg/kg
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
25 29 51 18 32 28 24 26 27 22 22 21 38 19 24 41 34 43 37 28
m m f m m m f f f m m m m m f f f f f m
163 169 155 176 176 178 155 161 150 150 170 171 158 184 159 150 140 151 147 168
57.4 69.4 50.2 59.6 68 54 46.8 58 44.6 49.4 55.6 57.6 62.3 75.4 53.6 36.2 53 59.4 67 68
21.6 24.3 20.8 19.4 21.9 17 19.5 22.4 20 21.8 19.2 19.7 24.9 22.2 21.2 16.1 27 25.5 31 24.1
yes yes yes no yes no yes yes yes no yes yes yes no yes yes yes yes yes yes
34.0 39.1 30.0 40.2 61.8 33.3 43.2 33.6 30.1 36.0 42.8 36.7 28.6 50.0 25.5 29.2 30.2 25.8 9 34.2
2.4. Statistical analysis
the problems of solid food ingestion in patients with cystinosis, using the TOMASS. We compared the results with normative data and a patient group in which dysphagia is a prominent symptom: myotonic dystrophy type 1 (MD1). MD1 is part of a group of inherited disorders called muscular dystrophies [5]. It is a multisystem disease, characterized by progressive myotonia (prolonged muscle contractions after use) and muscle weakness. In MD1, follow-up of dysphagia by a speechtherapist is usual care, while patients with cystinosis are hardly referred to speech-therapists [6].
We checked whether the variables were normally distributed using the Shapiro-Wilk test. In case of normally distributed variables, data of the two patient groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. The significance of both tests was set at p < .05. IBM SPSS statistics 22 software (IBM, Chicago) was used to perform the statistical analysis.
2. Methods
3. Results
2.1. Patients
3.1. Cystinosis patients
Twenty patients with nephropathic cystinosis (11 men and 9 women, range 19–51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 21–66 years) were included. Sex, age and body mass index were gathered as personal characteristics. All patients with cystinosis were treated with cysteamine. They reported no spontaneous complaints of dysphagia.
Table 1 shows the characteristics of the cystinosis patients. One patient was not able to perform the TOMASS. The variables ‘bites’, ‘swallows’ and ‘total time’ were not normally distributed. In Table 2, the TOMASS results of the cystinosis patients are compared to the healthy controls. It demonstrates that there is a significant difference in the number of bites (p < .01), masticatory cycles (t = −6.08, p < .01), swallows (p < .01) and total time (p < .01) between the normal values and healthy controls. The mean swallowing speed was 24.21 ml/s, which is normal. Looking at individual patients, only two patients (17 and 18) scored below 10 ml/s.
2.2. TOMASS Patients were asked to eat a standardized cracker (Albert Heijn Basic), ‘as quickly as is comfortably possible’. The number of bites, masticatory cycles, swallows per cracker and total time were registered. Before the start of the test, patients have to drink 150 ml water [4]. In our patients, this was achieved by examining the swallowing speed (see next paragraph). The normative data from 107 healthy adults between 20 and 70 years of age were derived from the Dutch database which was used for the development of the TOMASS [4].
Table 2 TOMASS results of the healthy adults, cystinosis patients and MD1 patients. The p-values indicate the difference between the patient group and healthy adults.
2.3. Swallowing speed To test the swallowing speed, a timed test of swallowing was used [7]. Patients have to drink 150 ml of water as quickly as possible, but they have to take care and stop if difficulties arise. The swallowing speed is supposed to be > 10 ml/s. Below 10 ml/s is an index of abnormal swallowing. 414
Healthy adults
Cystinosis
MD1
Mean (SD)
Mean (SD)
Mean (SD)
p-value
p-value
2.74 (1.20) p < .01 57.53 (28.11) p < .01 3.26 (1.59) p < .01 58.77 (28.89) p < .01
2.10 (0.99) p = .73 49.30 (15.69) p < .01 2.60 (0.84) p < .01 53.10 (15.85) p < .01
Bites (n)
1.97 (1.11)
Masticatory cycles (n)
34.39 (11.78)
Swallows (n)
1.65 (0.87)
Total time (sec)
28.53 (10.80)
Molecular Genetics and Metabolism 126 (2019) 413–415
A.E. van Rijssel et al.
3.2. Myotonic dystrophy
pharyngeal (pharyngeal pressure generation) stages of swallowing. Radiologic barium swallowing examination or videofluoroscopy is still seen as the gold standard for dysphagia assessment, but these examinations are more time consuming, more expansive and use radiation and contrast fluid. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients. We can regularly follow-up, even from relatively young ages, because the TOMASS is also validated in children [11]. If patients experience problems performing the TOMASS, referral to a speech therapist should be considered for education and awareness, to correct inadequate compensations and to learn to apply adequate compensations, like adjustments of food consistencies, consistently swallowing a bolus twice (double swallow) or drinking during or after a meal.
In MD1, the variable ‘total time’ was not normally distributed. In Table 2, the results of the patients with myotonic dystrophy are compared to the healthy controls. There is a significant difference in the number of masticatory cycles (t = −3.71), p < .01), swallows (t = −3.30, p < .01) and total time (p < .01) between the normal values and myotonic dystrophy patients. The was no significant difference between the two groups regarding the number of bites (t = −0.35, p = .73). 3.3. Cystinosis vs myotonic dystrophy Finally, we compared both patient groups. Only the variable ‘masticatory cycles’ was tested parametrically. There were no significant differences between the two patient groups regarding the number of bites (p = .18), masticatory cycles (t = 1.01, p = .32), swallows (p = .43) and total time (p = .84).
References
4. Discussion and conclusion
[1] E. Ivanova, M.G. de Leo, M.A. De Matteis, E. Levchenko, Cystinosis: clinical presentation, pathogenesis and treatment, Pediatr. Endocrinol. Rev. 12 (Suppl. 1) (2014) 176–184. [2] B.C. Sonies, E.F. Ekman, H.C. Andersson, et al., Swallowing dysfunction in nephropathic cystinosis, N. Engl. J. Med. 323 (1990) 565–570. [3] B.C. Sonies, P. Almajid, R. Kleta, et al., Swallowing dysfunction in 101 patients with nephropathic cystinosis, Medicine 147 (4) (2005) 242–250. [4] M.L. Huckabee, T. McINtosh, L. Fuller, et al., The test of masticating and swallowing solids (TOMASS): reliability, validity and international normative data, Int. J. Lang. Commun. Disord. 53 (1) (2018) 144–156. [5] G. Meola, R. Cardani, Myotonic dystrophies: an update on clinical aspects, genetic, pathology, and molecular pathomechanisms, Biochim. Biophys. Acta 1852 (2015) 594–606. [6] G.B. Langman, B.A. Barshop, G. Deschenes, et al., Controversies and research agenda in nephropathic cysstinosis: conclusions from a “Kidney Disease: improving global outcomes”(KDIGO) Controversies Conference, Kidney Int. 89 (2016) 1192–1203. [7] K.M. Nathadwarawala, J. Nicklin, Wiles Cm, A timed test of swallowing capacity for neurological patients, J. Neurol. Neurosurg. Psychiatry 55 (9) (1992) 822–825. [8] W.A. Gahl, G.F. Reed, J.G. Thoene, et al., Cysteamine therapy for children with nephropathic cystinosis, N. Engl. J. Med. 316 (1987) 971–977. [9] T.C. Markello, I.M. Bernardini, W.A. Gahl, Improved renal function in children with cystinosis treated with cysteamine, N. Engl. J. Med. 328 (1993) 1157–1162. [10] W.A. Gahl, J.Z. Balog, R. Kleta, Nephropathic cystinosis in adults: Natural history and effects of oral cysteamine therapy, Ann. Intern. Med. 147 (2007) 242–250. [11] U. Frank van de, L. Engel-Hoek, D. Nogueira, A. Schindler, S. Adams, M. Curry, M.L. Huckabee, International standardisation of the test of masticating and swallowing solids in children, J. Oral. Rehabil. 46 (2) (2019) 161–169.
Since patients with nephropathic cystinosis are currently treated with cysteamine, they have a better life expectancy [8,9]. When they become older, more extra–renal complications occur. One of these complications is swallowing dysfunction. In this study we demonstrated with a simple non-invasive test that cystinosis patients without clear complaints of dysphagia need more bites, more mastication cycles, more swallows and more time to eat a small cracker. In fact, they score equally to patients with MD1, in which dysphagia is a prominent symptom. In general, cystinosis patients have no difficulties in swallowing liquids. In cystinosis, one of the long-term major complications is myopathy, beginning with weakness and atrophy of the hand, extending to the upper extremities, the muscles involved swallowing, thoracic muscles and eventually the entire body's musculature. It was demonstrated that the frequency of myopathy is related to the duration of cysteamine therapy, but it is not known whether this represents a delay in onset of the myopathy or a complete prevention of it [10]. Clinicians taking care of patients with cystinosis should be aware of swallowing dysfunction in these patients. The TOMASS is the only noninvasive clinical tool to quantify solid food ingestion. It is supposed to identify especially problems in the oral (bolus preparation) and
415