Any new, sudden onset of tics or "tic-like" attacks should prompt consideration of Sydenham's chorea. The typical age range for Sydenham's chorea is 5-15yrs, with females more commonly affected, especially in adolescence, which fits with the group described [https://doi.org/10.1016/j.pediatrneurol.2009.11.015].
Neuropsychiatric signs, such as emotional lability, obsessive-compulsive signs, anxiety, and attention deficit often precede the chorea but may mistakenly lead to a presumption of a functional disorder. It can be difficult for non-specialists to distinguish different kinds of involuntary movements, and this may explain why delayed diagnosis is common in Sydenham's chorea [http://www.dx.doi.org/10.1136/archdischild-2015-308693].
The importance of establishing Sydenham's chorea as a cause is of course so that appropriate treatment can be given, including antibiotics and medication to control the chorea, but also to diagnose and treat co-existing rheumatic heart disease.
Have the authors consider the increased duration and nature of screen time as a trigger for these tic like disorders.
This would have implications for both prevention and treatment.
Is it correct that 'stress' as a trigger is one hypothesis only of functional symptoms that are not medically understood? Was there a comparison made for anxiety and stress is a matched group who did not developed these symptoms?
It is likely that the increase in social media posts and searches for tic disorders and Tourette's reflects their increased incidence rather than is causative. While is possible that the 'validation' does prolong or maintain the episodes it may be preferable to isolation and exclusion.
I read with interest the article ‘Covid-19 related increase in childhood tics and tic-like attacks’ by Heyman et al. It would seem the me that the premise that such a high increase in the prevalence of tics and Tourette’s in adolescent females is related to pandemic related stress is somewhat too simplistic. Their conclusion would seem very plausible in those with a predisposition or vulnerability to motor and phonic tics but including all these new cases under the umbrella of just ‘anxiety’ appears dismissive of other potential aetiological factors. The temporal relation to the Covid pandemic cannot simply be attributed to the psychological effects of pandemic related stress. Have any of these kids been tested for Covid antibodies to confirm or exclude that they have not been infected, possibly asymptomatically. Perhaps even more importantly have they been investigated for the presence of anti- neuronal antibodies which would be indicative of a possible autoimmune link that might explain this sudden surge in tics/Tourette’s. This PANS type possibility needs to be fully evaluated before attributing this increase in new onset of severe tics and tic-like attacks as a functional manifestation of the Covid-19 pandemic.
Many thanks for this analysis of a prospectively collected multi-centre data set, and for highlighting the unmet need for the development of a structured neurodevelopmental follow up pathway for children with heart disease.
In the sub category 'Neurodevelopmental outcome' under 'Methods' (page 264), the gross motor scores for children < 33 months mentions a scale of <39 as low. Should this not be <30 (instead of <39), given that 'low' is classified as less than 2 SD from 50 (and borderline is between 30 and 39)?
Thank you for sharing your experience. It echoes our current internal debate about parental participation. It would be so useful if you can share you one-page orientation leaflet about CEC, its purpose, composition and limitations as a supplementary attachment to this valuable letter.
Dear Editor,
We read with interest the report by Worth and colleagues on thyroid scintigraphy in infants with congenital hypothyroidism (CH). While their study is valuable in confirming the role of scintigraphy in locating the gland, we are concerned at the assertion that a gland in situ (GIS) constitutes a “subtype” of CH, and their placing it alongside defined entities of permanent CH such as athyreosis and ectopia. GIS is a purely descriptive term, encompassing both permanent and transient CH and comprising hypoplasia (eg TSH-receptor and PAX8 gene mutations), thyroid enlargement (classical dyshormonogenesis, iodine insufficiency) and normal-sized thyroid (multiple aetiologies). Infants with GIS include preterm and sick babies who are likely to have transient CH. It is not clear how many of the 20/37 GIS infants with transient CH in Worth's study were preterm/sick or had Down syndrome, and their prevalence figures of 28% for ectopia and 26% for “dysplasia” would be higher if expressed in the context of permanent rather than transient CH.
Worth et al have used scintigraphy to define GIS as small, normal and enlarged but do not state the criteria or detail their methodology. While scintigraphy reliably identifies thyroid ectopia, demonstrates intensity of isotope uptake and conveys an impression of gland size, ultrasound is superior in evaluation of size, vascularity (using colour Doppler) and detailed morphology2. Yet this modality is not discussed despi...
Dear Editor,
We read with interest the report by Worth and colleagues on thyroid scintigraphy in infants with congenital hypothyroidism (CH). While their study is valuable in confirming the role of scintigraphy in locating the gland, we are concerned at the assertion that a gland in situ (GIS) constitutes a “subtype” of CH, and their placing it alongside defined entities of permanent CH such as athyreosis and ectopia. GIS is a purely descriptive term, encompassing both permanent and transient CH and comprising hypoplasia (eg TSH-receptor and PAX8 gene mutations), thyroid enlargement (classical dyshormonogenesis, iodine insufficiency) and normal-sized thyroid (multiple aetiologies). Infants with GIS include preterm and sick babies who are likely to have transient CH. It is not clear how many of the 20/37 GIS infants with transient CH in Worth's study were preterm/sick or had Down syndrome, and their prevalence figures of 28% for ectopia and 26% for “dysplasia” would be higher if expressed in the context of permanent rather than transient CH.
Worth et al have used scintigraphy to define GIS as small, normal and enlarged but do not state the criteria or detail their methodology. While scintigraphy reliably identifies thyroid ectopia, demonstrates intensity of isotope uptake and conveys an impression of gland size, ultrasound is superior in evaluation of size, vascularity (using colour Doppler) and detailed morphology2. Yet this modality is not discussed despite the published evidence that combining ultrasound and scintigraphy enhances diagnostic accuracy.3,4
Finally, authors state that their study was not designed to investigate genetic aetiology. We believe that infants with suspected CH are entitled to a comprehensive and integrated assessment including venous thyroid function tests, serum thyroglobulin, scintigraphy to locate the thyroid, ultrasound imaging to determine morphology and estimate gland size, and molecular genetic analysis in selected cases. Most importantly, infants identified with GIS require critical follow up to determine whether their CH is permanent or transient 5, a management strategy which depends on thyroid imaging being performed in suspected CH. (327 words)
References
1. Worth C, Hird B, Tetlow L, Wright N, Patel L, Banerjee I. Arch Dis Child 2021;106:77–79.
2. Mansour C, Ouarezki Y, Jones JH, Green M, Stenhouse EJ, Irwin G, Hermanns P, Pohlenz J, Donaldson MDC. Determination of thyroid volume in infants with suspected congenital hypothyroidism—the limitations of both subjective and objective evaluation. BJR Open 2020; 2: 20200001. doi. org/ 10. 1259/ bjro. 20200001
3. Perry RJ, Maroo S, Maclellan AC, Jones JH, Donaldson MDC. Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning. Arch Dis Child 2006; 91: 972-976 doi.org/10.1136/adc.2006.096776
4. A. Lucas-Herald, J. Jones, M. Attaie, S. Maroo, D. Neumann, T. Bradley, J. Pohlenz, M. Donaldson. Predictive value of ultrasound and isotope thyroid scanning, alone and in combination, in the diagnosis of infants referred with TSH elevation on newborn screening. J Pediatr 2014;99:363-384. https://doi.org/10.1016/j.jpeds.2013.11.057
5. Léger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, et al. European Society for paediatric endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab 2014; 99: 363–84. doi: https://doi.org/10. 1210/jc.2013-1891
We were delighted to see Lucina highlighted positive data on Community Water Fluoridation (CWF) [1] Has Luciana seen the latest American Academy of Paediatrics (AAP) guideline on the issue? [2] They state that the AAP Standard of Care is Fluoride Varnish. However we have asked them why CWF isn’t the standard of care given the only objection they give for it is that it is a “controversial and highly emotional issue”. In the same paper they make suggestions including that paediatricians should:
1) Apply fluoride varnish
2) Know how to determine the concentration of fluoride in a child’s primary drinking water and determine the need for systemic supplements.
3) Advocate for water fluoridation in their local community.
UK paediatricians cannot apply fluoride varnish. UK paediatricians can identify concentrations of fluoride in the local drinking water using www.onepartpermillion.co.uk. They can prescribe fluoride supplements where there is need.
Until CWF is implemented does Lucina agree that these measures need promoting amongst UK Paediatricians?
References
1. Highlights from the literature Archives of Disease in Childhood 2020;105:1236.
2. Clark MB, Slayton RL for American Academy of Pediatrics Section on Oral Health. Pediatrics 146 (6):e2020034637
The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
The widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by a 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will h...
The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
The widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by a 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will have similar liver disease (5). Whatever genetic or epigenetic factors caused liver disease to manifest in the PiZ proband may be operative in the younger sibling. If the same is true of WD, then the risk of the newborn sibling developing liver disease is high. This conclusion will be difficult to prove because such infants should be monitored closely and treated early with zinc.
1. Sandahl TD, Laursen TL, Munk DE, Vilstrup H, Weiss KH, Ott P. The Prevalence of Wilson’s Disease: An Update. Hepatology. 2020 Feb 1;71(2):722–32.
2. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, et al. A genetic study of Wilson’s disease in the United Kingdom. Brain. 2013 May;136(5):1476–87.
3. Jang JH, Lee T, Bang S, Kim YE, Cho EH. Carrier frequency of Wilson’s disease in the Korean population: A DNA-based approach. J Hum Genet. 2017 Sep 1;62(9):815–8.
4. Wallace DF, Dooley JS. ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease. Hum Genet. 2020 Aug 1;139(8):1065–75.
5. Psacharopoulos HT, Mowat AP, Cook PJL, Carlile PA, Portmann B, Rodeck CH. Outcome of liver disease associated with αl antitrypsin deficiency (PiZ): Implications for genetic counselling and antenatal diagnosis. Arch Dis Child. 1983;58(11):882–7.
Acute haemorrhagic oedema of infancy, also termed cockade purpura with edema or Finkelstein-Seidlmayer disease, is a rather uncommon small-vessel leukocytoclastic vasculitis. It characteristically affects children 4 weeks to 23 months of age, is skin-limited, spontaneously recovers within 3 weeks, and does not recur. O'Connor C et al [1]. recently documented the distinctive features of acute haemorrhagic oedema in a 23-day-old male infant with fever, rhinorrhoea, conjunctivitis and cough. The authors concluded that acute haemorrhagic oedema has never previously been reported in neonates, with the exception of a female newborn infant noted to have this vasculitis at birth [2].
Stimulated by the fascinating report by O'Connor C et al. [1], we analyzed the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID, which includes all articles on acute haemorrhagic oedema. In the mentioned database, we found 6 further cases (4 males and 2 female patient) of this vasculitis in subjects less than 4 weeks of age, including 4 familial cases [3-5].
It is therefore concluded that acute haemorrhagic oedema has been so far documented in a total of 8 patients (5 males and 3 female patient) less less than 4 weeks of age. In this age group, this vasculitis is uncommon but not exceptional and may affect 2 or more members of the same family.
References
1. O’Connor C, Bux D, O’Connell M. Acute haemorrhagic oedema of infancy: first report...
Acute haemorrhagic oedema of infancy, also termed cockade purpura with edema or Finkelstein-Seidlmayer disease, is a rather uncommon small-vessel leukocytoclastic vasculitis. It characteristically affects children 4 weeks to 23 months of age, is skin-limited, spontaneously recovers within 3 weeks, and does not recur. O'Connor C et al [1]. recently documented the distinctive features of acute haemorrhagic oedema in a 23-day-old male infant with fever, rhinorrhoea, conjunctivitis and cough. The authors concluded that acute haemorrhagic oedema has never previously been reported in neonates, with the exception of a female newborn infant noted to have this vasculitis at birth [2].
Stimulated by the fascinating report by O'Connor C et al. [1], we analyzed the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID, which includes all articles on acute haemorrhagic oedema. In the mentioned database, we found 6 further cases (4 males and 2 female patient) of this vasculitis in subjects less than 4 weeks of age, including 4 familial cases [3-5].
It is therefore concluded that acute haemorrhagic oedema has been so far documented in a total of 8 patients (5 males and 3 female patient) less less than 4 weeks of age. In this age group, this vasculitis is uncommon but not exceptional and may affect 2 or more members of the same family.
References
1. O’Connor C, Bux D, O’Connell M. Acute haemorrhagic oedema of infancy: first report of a rare small vessel vasculitis in the neonatal period. Arch Dis Child 2020: Epub ahead of print. doi:10.1136/archdischild-2020-319739.
2. Cunningham BB, Caro WA, Eramo LR. Neonatal acute hemorrhagic edema of childhood: case report and review of the English-language literature. Pediatr Dermatol 1996;13:39-44.
3. Ballona R. Pápulas purpúricas en récien nacido. Dermatol Peru 2002;12:231-3.
4. Checa Rodríguez R, Carabaño Aguado I, Álvarez Fernández B. Edema agudo hemorrágico en un neonato. Pediatr Aten Primaria 2015;17:151-3.
5. Ostini A, Ramelli GP, Mainetti C, Bianchetti MG, Ferrarini A. Recurrent Finkelstein-Seidlmayer disease in four first-degree relatives. Acta Derm Venereol 2015;95:622-3.
The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
The widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will hav...
The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
The widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will have similar liver disease (5). Whatever genetic or epigenetic factors caused liver disease to manifest in the PiZ proband may be operative in the younger sibling. If the same is true of WD, then the risk of the newborn sibling developing liver disease is high. This conclusion will be difficult to prove because such infants should be monitored closely and treated early with zinc.
1. Sandahl TD, Laursen TL, Munk DE, Vilstrup H, Weiss KH, Ott P. The Prevalence of Wilson’s Disease: An Update. Hepatology. 2020 Feb 1;71(2):722–32.
2. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, et al. A genetic study of Wilson’s disease in the United Kingdom. Brain. 2013 May;136(5):1476–87.
3. Jang JH, Lee T, Bang S, Kim YE, Cho EH. Carrier frequency of Wilson’s disease in the Korean population: A DNA-based approach. J Hum Genet. 2017 Sep 1;62(9):815–8.
4. Wallace DF, Dooley JS. ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease. Hum Genet. 2020 Aug 1;139(8):1065–75.
5. Psacharopoulos HT, Mowat AP, Cook PJL, Carlile PA, Portmann B, Rodeck CH. Outcome of liver disease associated with αl antitrypsin deficiency (PiZ): Implications for genetic counselling and antenatal diagnosis. Arch Dis Child. 1983;58(11):882–7.
Any new, sudden onset of tics or "tic-like" attacks should prompt consideration of Sydenham's chorea. The typical age range for Sydenham's chorea is 5-15yrs, with females more commonly affected, especially in adolescence, which fits with the group described [https://doi.org/10.1016/j.pediatrneurol.2009.11.015].
Neuropsychiatric signs, such as emotional lability, obsessive-compulsive signs, anxiety, and attention deficit often precede the chorea but may mistakenly lead to a presumption of a functional disorder. It can be difficult for non-specialists to distinguish different kinds of involuntary movements, and this may explain why delayed diagnosis is common in Sydenham's chorea [http://www.dx.doi.org/10.1136/archdischild-2015-308693].
The importance of establishing Sydenham's chorea as a cause is of course so that appropriate treatment can be given, including antibiotics and medication to control the chorea, but also to diagnose and treat co-existing rheumatic heart disease.
Have the authors consider the increased duration and nature of screen time as a trigger for these tic like disorders.
This would have implications for both prevention and treatment.
Is it correct that 'stress' as a trigger is one hypothesis only of functional symptoms that are not medically understood? Was there a comparison made for anxiety and stress is a matched group who did not developed these symptoms?
It is likely that the increase in social media posts and searches for tic disorders and Tourette's reflects their increased incidence rather than is causative. While is possible that the 'validation' does prolong or maintain the episodes it may be preferable to isolation and exclusion.
I read with interest the article ‘Covid-19 related increase in childhood tics and tic-like attacks’ by Heyman et al. It would seem the me that the premise that such a high increase in the prevalence of tics and Tourette’s in adolescent females is related to pandemic related stress is somewhat too simplistic. Their conclusion would seem very plausible in those with a predisposition or vulnerability to motor and phonic tics but including all these new cases under the umbrella of just ‘anxiety’ appears dismissive of other potential aetiological factors. The temporal relation to the Covid pandemic cannot simply be attributed to the psychological effects of pandemic related stress. Have any of these kids been tested for Covid antibodies to confirm or exclude that they have not been infected, possibly asymptomatically. Perhaps even more importantly have they been investigated for the presence of anti- neuronal antibodies which would be indicative of a possible autoimmune link that might explain this sudden surge in tics/Tourette’s. This PANS type possibility needs to be fully evaluated before attributing this increase in new onset of severe tics and tic-like attacks as a functional manifestation of the Covid-19 pandemic.
Dear Authors
Many thanks for this analysis of a prospectively collected multi-centre data set, and for highlighting the unmet need for the development of a structured neurodevelopmental follow up pathway for children with heart disease.
In the sub category 'Neurodevelopmental outcome' under 'Methods' (page 264), the gross motor scores for children < 33 months mentions a scale of <39 as low. Should this not be <30 (instead of <39), given that 'low' is classified as less than 2 SD from 50 (and borderline is between 30 and 39)?
Many thanks for clarifying.
Kind regards.
Thank you for sharing your experience. It echoes our current internal debate about parental participation. It would be so useful if you can share you one-page orientation leaflet about CEC, its purpose, composition and limitations as a supplementary attachment to this valuable letter.
Dear Editor,
Show MoreWe read with interest the report by Worth and colleagues on thyroid scintigraphy in infants with congenital hypothyroidism (CH). While their study is valuable in confirming the role of scintigraphy in locating the gland, we are concerned at the assertion that a gland in situ (GIS) constitutes a “subtype” of CH, and their placing it alongside defined entities of permanent CH such as athyreosis and ectopia. GIS is a purely descriptive term, encompassing both permanent and transient CH and comprising hypoplasia (eg TSH-receptor and PAX8 gene mutations), thyroid enlargement (classical dyshormonogenesis, iodine insufficiency) and normal-sized thyroid (multiple aetiologies). Infants with GIS include preterm and sick babies who are likely to have transient CH. It is not clear how many of the 20/37 GIS infants with transient CH in Worth's study were preterm/sick or had Down syndrome, and their prevalence figures of 28% for ectopia and 26% for “dysplasia” would be higher if expressed in the context of permanent rather than transient CH.
Worth et al have used scintigraphy to define GIS as small, normal and enlarged but do not state the criteria or detail their methodology. While scintigraphy reliably identifies thyroid ectopia, demonstrates intensity of isotope uptake and conveys an impression of gland size, ultrasound is superior in evaluation of size, vascularity (using colour Doppler) and detailed morphology2. Yet this modality is not discussed despi...
Dear Editor
We were delighted to see Lucina highlighted positive data on Community Water Fluoridation (CWF) [1] Has Luciana seen the latest American Academy of Paediatrics (AAP) guideline on the issue? [2] They state that the AAP Standard of Care is Fluoride Varnish. However we have asked them why CWF isn’t the standard of care given the only objection they give for it is that it is a “controversial and highly emotional issue”. In the same paper they make suggestions including that paediatricians should:
1) Apply fluoride varnish
2) Know how to determine the concentration of fluoride in a child’s primary drinking water and determine the need for systemic supplements.
3) Advocate for water fluoridation in their local community.
UK paediatricians cannot apply fluoride varnish. UK paediatricians can identify concentrations of fluoride in the local drinking water using www.onepartpermillion.co.uk. They can prescribe fluoride supplements where there is need.
Until CWF is implemented does Lucina agree that these measures need promoting amongst UK Paediatricians?
References
1. Highlights from the literature Archives of Disease in Childhood 2020;105:1236.
2. Clark MB, Slayton RL for American Academy of Pediatrics Section on Oral Health. Pediatrics 146 (6):e2020034637
The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
Show MoreThe widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by a 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will h...
Acute haemorrhagic oedema of infancy, also termed cockade purpura with edema or Finkelstein-Seidlmayer disease, is a rather uncommon small-vessel leukocytoclastic vasculitis. It characteristically affects children 4 weeks to 23 months of age, is skin-limited, spontaneously recovers within 3 weeks, and does not recur. O'Connor C et al [1]. recently documented the distinctive features of acute haemorrhagic oedema in a 23-day-old male infant with fever, rhinorrhoea, conjunctivitis and cough. The authors concluded that acute haemorrhagic oedema has never previously been reported in neonates, with the exception of a female newborn infant noted to have this vasculitis at birth [2].
Stimulated by the fascinating report by O'Connor C et al. [1], we analyzed the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID, which includes all articles on acute haemorrhagic oedema. In the mentioned database, we found 6 further cases (4 males and 2 female patient) of this vasculitis in subjects less than 4 weeks of age, including 4 familial cases [3-5].
It is therefore concluded that acute haemorrhagic oedema has been so far documented in a total of 8 patients (5 males and 3 female patient) less less than 4 weeks of age. In this age group, this vasculitis is uncommon but not exceptional and may affect 2 or more members of the same family.
References
Show More1. O’Connor C, Bux D, O’Connell M. Acute haemorrhagic oedema of infancy: first report...
The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
Show MoreThe widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will hav...
Pages