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Papers by Victor Mercieca
Clinical and Experimental Dermatology, 2020
A 17-month old boy was referred to the genetic clinic in view of anodontia, hypohidrosis, scalp h... more A 17-month old boy was referred to the genetic clinic in view of anodontia, hypohidrosis, scalp hypotrichosis, atrichia of the eyelashes, xerotic skin and a short columella. A diagnosis of X-Linked hypohidrotic ectodermal dysplasia (XLHED) was considered. The boy was born to healthy non-consanguineous parents of Maltese-Caucasian ethnicity at 38 weeks by emergency lower segment Caesarean section in view of fetal decelerations in the setting of documented intrauterine growth restriction (birth weight was 2.49kg [2.5th centile for age]). The genetic family history of the patient was unremarkable.
ABSTRACT TITLE: Large deletion in the EPCAM gene responsible for the milder phenotype of congenit... more ABSTRACT TITLE: Large deletion in the EPCAM gene responsible for the milder phenotype of congenital tufting enteropathy AUTHORS (LAST NAME, FIRST NAME): Gerada ABSTRACT BODY: Abstract Body: Introduction: A number of point mutations within the EPCAM gene have been found to be responsible
Journal of Clinical & Experimental Cardiology, 2010
Introduction: Echocardiography is the modality of choice for investigation of suspected congenita... more Introduction: Echocardiography is the modality of choice for investigation of suspected congenital or acquired heart disease. It may be used as part of the screening process for suspected heart disease in childhood after the incidental fi nding of a murmur, even if this is deemed to be an innocent murmur by the referring clinician. However some studies have shown that parents may misunderstand the implications of a normal test and may persistently restrict their child's activity even after a normal echocardiogram. The second part of this study prospectively audited echocardiography requests for non-elective (urgent) echocardiograms, in the setting of a regional hospital that serves an entire captive island population for the period 2007. An analysis of parental understanding of a normal echocardiogram was also carried out. Methods: All normal and all urgent echocardiograms were prospectively collected for the 2007 Parents were administered a telephone questionnaire with regard to their understanding of a normal echocardiogram, after one month. Information collected also included age of patient, delay from request to actual procedure, actual indication and echocardiographic outcome (diagnosis). Results: 88 non-elective echocardiograms were performed with a bimodal age distribution ranging from 1 hour to 50 years. The majority were infants. 6 patients were aged over 14 years. The delay to the actual performance of the echocardiogram ranged from 2 hours to 20 days, with a mean of 2.8 days and a median of 1 day. The outcome was completely normal in 35 individuals, physiological for age in 14 individuals (total normal of 49-55%) and abnormal in 39. 89 normal echocardiograms were included. 79 parents stated that they were fully satisfi ed with the explanation and implications of a normal echocardiogram and 10 were almost fully satisfi ed. No signifi cant differences could be found between these two groups. A hard copy was more likely to reassure the parents, but not at a statistically signifi cant level. Only 77 had a full explanation with regard to the implications of an innocent murmur with echocardiographic confi rmation but this too did not affect parental reassurance. Discussion: 88 non-elective echocardiograms accounted for 10% of the total paediatric echocardiogram referrals for the period 2007, with a signifi cant pickup rate for pathological lesions. For normal echocardiography examinations, this study confi rms that parents are satisfi ed with an explanation of the implications of a normal echocardiogram. Our service can be improved by providing a full explanation to all parents and by adopting the policy of giving a hard copy of the normal report to all parents. This study prospectively analysed two facets of paediatric echocardiography: 1. An audit of requests for the first two groups as above, that is, non-elective (urgent) echocardiograms, in the setting of a regional hospital that serves an entire captive island population [6]. 2. This study also prospectively analysed the degree of parental understanding of a normal echocardiogram. Methods Audit of urgent echocardiography referrals Data from all individuals referred for echocardiogram to the only
Pediatric Cardiology, 2001
It is known that atrial septal defects of the secundum type and ventricular septal defects may un... more It is known that atrial septal defects of the secundum type and ventricular septal defects may undergo spontaneous closure. However, it is not well recognized that atrioventricular septal defects may infrequently also undergo spontaneous resolution. We report one case of complete atrioventricular septal defect that underwent spontaneous closure of the ventricular component. We also describe one case of partial atrioventricular septal defect with almost complete spontaneous resolution of the interatrial communication. Presence of shunting across the defects is demonstrated by color Doppler echocardiography, along with later absence of shunting. The rate of spontaneous resolution is estimated.
The Journal of Pediatrics, 1988
Images in paediatric cardiology, 2004
We present a patient with tetralogy of Fallot who developed bilateral branch pulmonary artery ste... more We present a patient with tetralogy of Fallot who developed bilateral branch pulmonary artery stenosis following surgical repair that was refractory to balloon dilatation. Simultaneous stenting of both pulmonary arteries produced a good result.
Congenital heart disease (CHO) is the commonest congenital malformation, and ventricular septal d... more Congenital heart disease (CHO) is the commonest congenital malformation, and ventricular septal derect (VSD) and atrial septal derect (ASO) are the commonest rorms or CHO. This study was undertaken to determine rates or spontaneous closure or lesions diagnosed at echocardiography after detection or a murmur in Maltese patients born in 1990-94. A significant excess or ASO and VSO was round in Malta, and this was attributed to early echocardiographic diagnosis or small derects, prior to spontaneous closure. A high spontaneous closure rate was round ror both ASO and VSO. Rate or closure ror both derects was initially high, and tapered orr at about 5 to 7 years or age ror both lesions. ASOs in excess or 8 mm in diameter at presentation also underwent spontaneous resolution, which is contrary to the known natural history or these derects. Larger VS Os were shown to have a smaller likelihood or closing (p=0.04). Parents and patients can be reassured that spontaneous closure is very likely...
29 Abstract Objective: To compare the clinical acumen of paediatric cardiovascular examination be... more 29 Abstract Objective: To compare the clinical acumen of paediatric cardiovascular examination between various hospital paediatrician grades. Design: Prospective data collection of clinical and echocardiography findings on paediatric echocardiography referrals. Setting and patients: All paediatric patients (birth 14 years) referred for echocardiography, in a regional hospital catering for the island population of Malta. Echocardiography was carried out by three paediatricians with tertiary training in this technique. Main outcome measures: Pre-echocardiography clinical diagnoses were compared with echocardiography results according to grade of referring hospital doctor (ranging from houseman to consultant). Both normal and abnormal hearts at echocardiography were included. Results: Echocardiographers had the highest clinical accuracy and the highest attempts at reaching a clinical diagnosis. Accuracy and attempts at diagnosis decreased as doctor’s hospital grade decreased, from cons...
Journal of Pediatric Gastroenterology and Nutrition
To review long-term outcome of Intestinal Epithelial Dysplasia(IED)/tufting enteropathy(TE) patie... more To review long-term outcome of Intestinal Epithelial Dysplasia(IED)/tufting enteropathy(TE) patients treated with parenteral nutrition(PN) at home managed by an intestinal failure(IF) rehabilitation service METHODS:: Infants presenting from 1986-2010 with IF, and TE histology were retrospectively reviewed for up to 30 years. Data collected included: outcome, presentation, nutrition(parenteral/enteral), country of residence, race, EpCAM gene, growth, bone age, occupation. 13 patients (6 male) in Malta and the UK with TE histology were established on home PN. Survival was 100% for UK children and 92% overall (one death aged 13 months). Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements reduced with increasing age and <7 infusions/week were needed by 10/12, 83% by 10 years, 6/8, 75% who had reached 15 years, 5/7, 71% who had reached 20 and all 4, 100% >25 years. Two/12 cases weaned from PN by 10 years, 1/8 by 15 years, 3/7 by 20 years and 3/4 or 75% >25 years. Six Maltese patients homozygous for the same EPCAM gene abnormality had a similar outcome to the other cases.Weight, height, bone mineralisation, bone age and IGF-1 levels were low, but improved with age. Patients achieved educational levels of parents and were employed. IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant.
Pediatric Neurology, 2001
The treatment of acquired cobalamin deficiency in infants may result in the development of a synd... more The treatment of acquired cobalamin deficiency in infants may result in the development of a syndrome defined by temporary involuntary myoclonic movements. A patient with an inborn error of metabolism resulting in transcobalmin 2 deficiency who was treated with cobalamin and then developed this syndrome is presented. Neurologic investigations were normal. The continuance of cobalamin and avoidance of antiepileptic drugs is recommended. To our knowledge this is the first such case.
Gastroenterology, 2015
ABSTRACT INTRODUCTION: A number of point mutations within the EPCAM gene have been found to be re... more ABSTRACT INTRODUCTION: A number of point mutations within the EPCAM gene have been found to be responsible for congenital tufting enteropathy (CTE). We previously described a milder phenotype of CTE in a cohort of Maltese patients. EpCAM staining was negative in the whole cohort, suggesting a defective EPCAM gene in the milder phenotype. AIMS & METHODS: Aims: To identify the underlying genetic abnormality within the EPCAM gene responsible for the milder CTE. Methods: In the period 1985 – 2012, eight Maltese patients with CTE from six unrelated families were retrospectively identified. Genomic DNA was extracted from peripheral blood. Primers for all nine exons within the EPCAM gene were designed and optimized. PCR products were amplified and sequenced. To sequence exon 4 – exon 6 region, the PCR product was purified from the gel and ligated in a TA Vector. The ligated products were transformed into DH5α bacteria and cultured on ampicillin-containing agar plates. The cultured DNA was extracted and sequenced. All DNA sequences were compared with controls. Unaffected family members (parents) and healthy controls were screened for the deletion. RESULTS: Genetic analysis of the EPCAM gene in Maltese CTE patients revealed a novel homozygous 1773bp deletion in seven patients, starting from 1170bp downstream of exon 4, up to 721bp upstream of exon 6, resulting in complete deletion of exon 5. The remaining patient was a heterozygote for the deletion. The mutant homozygous variant resulted in a frameshift, introducing 23 novel amino acids, formation of a premature stop codon, p.Ala164Metfs*24. loss of the transmembrane domain and complete lack of EpCAM protein within the intestinal epithelium. Three sets of parents of 3 affected patients were all heterozygous for this deletion. 98 out of 100 healthy controls tested were homozygous wild type and two (2%) were heterozygous for the deletion. CONCLUSION: This novel large deletion within the EPCAM gene was found to be responsible for the milder phenotype of Maltese CTE patients. The heterozygous mutation of the patients' parents confirms the autosomal recessive pattern of inheritance of CTE. This genetic deletion present in all patients implies a founder effect and we propose this as the first genotype-phenotype correlation in isolated intestinal TE patients. REFERENCES: 1. Gerada J, Scerri C, DeGaetano J, Hill S, Vassallo M, Attard TM. Epithelial EpCAM expression does not correlate with intestinal absorptive function in the milder phenotype of tufting enteropathy GUT. 2012;61(Suppl 3): A75
Clinical and Experimental Dermatology, 2020
A 17-month old boy was referred to the genetic clinic in view of anodontia, hypohidrosis, scalp h... more A 17-month old boy was referred to the genetic clinic in view of anodontia, hypohidrosis, scalp hypotrichosis, atrichia of the eyelashes, xerotic skin and a short columella. A diagnosis of X-Linked hypohidrotic ectodermal dysplasia (XLHED) was considered. The boy was born to healthy non-consanguineous parents of Maltese-Caucasian ethnicity at 38 weeks by emergency lower segment Caesarean section in view of fetal decelerations in the setting of documented intrauterine growth restriction (birth weight was 2.49kg [2.5th centile for age]). The genetic family history of the patient was unremarkable.
ABSTRACT TITLE: Large deletion in the EPCAM gene responsible for the milder phenotype of congenit... more ABSTRACT TITLE: Large deletion in the EPCAM gene responsible for the milder phenotype of congenital tufting enteropathy AUTHORS (LAST NAME, FIRST NAME): Gerada ABSTRACT BODY: Abstract Body: Introduction: A number of point mutations within the EPCAM gene have been found to be responsible
Journal of Clinical & Experimental Cardiology, 2010
Introduction: Echocardiography is the modality of choice for investigation of suspected congenita... more Introduction: Echocardiography is the modality of choice for investigation of suspected congenital or acquired heart disease. It may be used as part of the screening process for suspected heart disease in childhood after the incidental fi nding of a murmur, even if this is deemed to be an innocent murmur by the referring clinician. However some studies have shown that parents may misunderstand the implications of a normal test and may persistently restrict their child's activity even after a normal echocardiogram. The second part of this study prospectively audited echocardiography requests for non-elective (urgent) echocardiograms, in the setting of a regional hospital that serves an entire captive island population for the period 2007. An analysis of parental understanding of a normal echocardiogram was also carried out. Methods: All normal and all urgent echocardiograms were prospectively collected for the 2007 Parents were administered a telephone questionnaire with regard to their understanding of a normal echocardiogram, after one month. Information collected also included age of patient, delay from request to actual procedure, actual indication and echocardiographic outcome (diagnosis). Results: 88 non-elective echocardiograms were performed with a bimodal age distribution ranging from 1 hour to 50 years. The majority were infants. 6 patients were aged over 14 years. The delay to the actual performance of the echocardiogram ranged from 2 hours to 20 days, with a mean of 2.8 days and a median of 1 day. The outcome was completely normal in 35 individuals, physiological for age in 14 individuals (total normal of 49-55%) and abnormal in 39. 89 normal echocardiograms were included. 79 parents stated that they were fully satisfi ed with the explanation and implications of a normal echocardiogram and 10 were almost fully satisfi ed. No signifi cant differences could be found between these two groups. A hard copy was more likely to reassure the parents, but not at a statistically signifi cant level. Only 77 had a full explanation with regard to the implications of an innocent murmur with echocardiographic confi rmation but this too did not affect parental reassurance. Discussion: 88 non-elective echocardiograms accounted for 10% of the total paediatric echocardiogram referrals for the period 2007, with a signifi cant pickup rate for pathological lesions. For normal echocardiography examinations, this study confi rms that parents are satisfi ed with an explanation of the implications of a normal echocardiogram. Our service can be improved by providing a full explanation to all parents and by adopting the policy of giving a hard copy of the normal report to all parents. This study prospectively analysed two facets of paediatric echocardiography: 1. An audit of requests for the first two groups as above, that is, non-elective (urgent) echocardiograms, in the setting of a regional hospital that serves an entire captive island population [6]. 2. This study also prospectively analysed the degree of parental understanding of a normal echocardiogram. Methods Audit of urgent echocardiography referrals Data from all individuals referred for echocardiogram to the only
Pediatric Cardiology, 2001
It is known that atrial septal defects of the secundum type and ventricular septal defects may un... more It is known that atrial septal defects of the secundum type and ventricular septal defects may undergo spontaneous closure. However, it is not well recognized that atrioventricular septal defects may infrequently also undergo spontaneous resolution. We report one case of complete atrioventricular septal defect that underwent spontaneous closure of the ventricular component. We also describe one case of partial atrioventricular septal defect with almost complete spontaneous resolution of the interatrial communication. Presence of shunting across the defects is demonstrated by color Doppler echocardiography, along with later absence of shunting. The rate of spontaneous resolution is estimated.
The Journal of Pediatrics, 1988
Images in paediatric cardiology, 2004
We present a patient with tetralogy of Fallot who developed bilateral branch pulmonary artery ste... more We present a patient with tetralogy of Fallot who developed bilateral branch pulmonary artery stenosis following surgical repair that was refractory to balloon dilatation. Simultaneous stenting of both pulmonary arteries produced a good result.
Congenital heart disease (CHO) is the commonest congenital malformation, and ventricular septal d... more Congenital heart disease (CHO) is the commonest congenital malformation, and ventricular septal derect (VSD) and atrial septal derect (ASO) are the commonest rorms or CHO. This study was undertaken to determine rates or spontaneous closure or lesions diagnosed at echocardiography after detection or a murmur in Maltese patients born in 1990-94. A significant excess or ASO and VSO was round in Malta, and this was attributed to early echocardiographic diagnosis or small derects, prior to spontaneous closure. A high spontaneous closure rate was round ror both ASO and VSO. Rate or closure ror both derects was initially high, and tapered orr at about 5 to 7 years or age ror both lesions. ASOs in excess or 8 mm in diameter at presentation also underwent spontaneous resolution, which is contrary to the known natural history or these derects. Larger VS Os were shown to have a smaller likelihood or closing (p=0.04). Parents and patients can be reassured that spontaneous closure is very likely...
29 Abstract Objective: To compare the clinical acumen of paediatric cardiovascular examination be... more 29 Abstract Objective: To compare the clinical acumen of paediatric cardiovascular examination between various hospital paediatrician grades. Design: Prospective data collection of clinical and echocardiography findings on paediatric echocardiography referrals. Setting and patients: All paediatric patients (birth 14 years) referred for echocardiography, in a regional hospital catering for the island population of Malta. Echocardiography was carried out by three paediatricians with tertiary training in this technique. Main outcome measures: Pre-echocardiography clinical diagnoses were compared with echocardiography results according to grade of referring hospital doctor (ranging from houseman to consultant). Both normal and abnormal hearts at echocardiography were included. Results: Echocardiographers had the highest clinical accuracy and the highest attempts at reaching a clinical diagnosis. Accuracy and attempts at diagnosis decreased as doctor’s hospital grade decreased, from cons...
Journal of Pediatric Gastroenterology and Nutrition
To review long-term outcome of Intestinal Epithelial Dysplasia(IED)/tufting enteropathy(TE) patie... more To review long-term outcome of Intestinal Epithelial Dysplasia(IED)/tufting enteropathy(TE) patients treated with parenteral nutrition(PN) at home managed by an intestinal failure(IF) rehabilitation service METHODS:: Infants presenting from 1986-2010 with IF, and TE histology were retrospectively reviewed for up to 30 years. Data collected included: outcome, presentation, nutrition(parenteral/enteral), country of residence, race, EpCAM gene, growth, bone age, occupation. 13 patients (6 male) in Malta and the UK with TE histology were established on home PN. Survival was 100% for UK children and 92% overall (one death aged 13 months). Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements reduced with increasing age and <7 infusions/week were needed by 10/12, 83% by 10 years, 6/8, 75% who had reached 15 years, 5/7, 71% who had reached 20 and all 4, 100% >25 years. Two/12 cases weaned from PN by 10 years, 1/8 by 15 years, 3/7 by 20 years and 3/4 or 75% >25 years. Six Maltese patients homozygous for the same EPCAM gene abnormality had a similar outcome to the other cases.Weight, height, bone mineralisation, bone age and IGF-1 levels were low, but improved with age. Patients achieved educational levels of parents and were employed. IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant.
Pediatric Neurology, 2001
The treatment of acquired cobalamin deficiency in infants may result in the development of a synd... more The treatment of acquired cobalamin deficiency in infants may result in the development of a syndrome defined by temporary involuntary myoclonic movements. A patient with an inborn error of metabolism resulting in transcobalmin 2 deficiency who was treated with cobalamin and then developed this syndrome is presented. Neurologic investigations were normal. The continuance of cobalamin and avoidance of antiepileptic drugs is recommended. To our knowledge this is the first such case.
Gastroenterology, 2015
ABSTRACT INTRODUCTION: A number of point mutations within the EPCAM gene have been found to be re... more ABSTRACT INTRODUCTION: A number of point mutations within the EPCAM gene have been found to be responsible for congenital tufting enteropathy (CTE). We previously described a milder phenotype of CTE in a cohort of Maltese patients. EpCAM staining was negative in the whole cohort, suggesting a defective EPCAM gene in the milder phenotype. AIMS & METHODS: Aims: To identify the underlying genetic abnormality within the EPCAM gene responsible for the milder CTE. Methods: In the period 1985 – 2012, eight Maltese patients with CTE from six unrelated families were retrospectively identified. Genomic DNA was extracted from peripheral blood. Primers for all nine exons within the EPCAM gene were designed and optimized. PCR products were amplified and sequenced. To sequence exon 4 – exon 6 region, the PCR product was purified from the gel and ligated in a TA Vector. The ligated products were transformed into DH5α bacteria and cultured on ampicillin-containing agar plates. The cultured DNA was extracted and sequenced. All DNA sequences were compared with controls. Unaffected family members (parents) and healthy controls were screened for the deletion. RESULTS: Genetic analysis of the EPCAM gene in Maltese CTE patients revealed a novel homozygous 1773bp deletion in seven patients, starting from 1170bp downstream of exon 4, up to 721bp upstream of exon 6, resulting in complete deletion of exon 5. The remaining patient was a heterozygote for the deletion. The mutant homozygous variant resulted in a frameshift, introducing 23 novel amino acids, formation of a premature stop codon, p.Ala164Metfs*24. loss of the transmembrane domain and complete lack of EpCAM protein within the intestinal epithelium. Three sets of parents of 3 affected patients were all heterozygous for this deletion. 98 out of 100 healthy controls tested were homozygous wild type and two (2%) were heterozygous for the deletion. CONCLUSION: This novel large deletion within the EPCAM gene was found to be responsible for the milder phenotype of Maltese CTE patients. The heterozygous mutation of the patients' parents confirms the autosomal recessive pattern of inheritance of CTE. This genetic deletion present in all patients implies a founder effect and we propose this as the first genotype-phenotype correlation in isolated intestinal TE patients. REFERENCES: 1. Gerada J, Scerri C, DeGaetano J, Hill S, Vassallo M, Attard TM. Epithelial EpCAM expression does not correlate with intestinal absorptive function in the milder phenotype of tufting enteropathy GUT. 2012;61(Suppl 3): A75