Uniparental disomy screen of Irish rare disorder cohort unmasks homozygous variants of clinical significance in the TMCO1 and PRKRA genes.

A uniparental disomy (UPD) screen using whole genome sequencing (WGS) data from 164 trios with rare disorders in the Irish population was performed to identify large runs of homozygosity of uniparental origin that may harbour deleterious recessive variants. Three instances of whole chromosome uniparental isodisomy (UPiD) were identified: one case of maternal isodisomy of chromosome 1 and two cases of paternal isodisomy of chromosome 2. We identified deleterious homozygous variants on isodisomic chromosomes in two probands: a novel p (Glu59ValfsTer20) variant in TMCO1, and a p (Pro222Leu) variant in PRKRA, respectively. The overall prevalence of whole chromosome UPiD in our cohort was 1 in 55 births, compared to 1 in ∼7,500 births in the general population, suggesting a higher frequency of UPiD in rare disease cohorts. As a distinct mechanism underlying homozygosity compared to biallelic inheritance, the identification of UPiD has important implications for family planning and cascade testing. Our study demonstrates that UPD screening may improve diagnostic yields by prioritising UPiD chromosomes during WGS analysis.

Hepatic Cystic Echinococcosis (Hydatid Cyst) in a Six Year Old.

Presentation To describe a case of cystic echinococcosis (CE) in a previously healthy child and review epidemiology of CE in Ireland. Diagnosis A previously healthy 6 year old girl was found to have a cystic lesion in the right lobe of her liver. Serology for Echinococcus granulosus was positive, and radiological features were suggestive of CE. Treatment The patient was pre-treated with anti-helminthic medications before undergoing a liver segmentectomy to remove the cyst, and received further treatment with albendazole after surgery. Histological findings were consistent with CE due to E. granulosus, likely acquired during travel to continental Europe. Conclusion CE should be considered in the differential of children with asymptomatic cysts in the liver and/or lung, and a travel history elucidated in such cases.

Listeria Meningitis in an Immunocompetent Child: Case Report and Literature Review

We present a case of a 23 month-old boy presenting with fever, irritability and diarrhea who subsequently developed symptoms of photophobia and lethargy. Cerebrospinal fluid culture grew Listeria monocytogenes. Immunology investigations were normal. This patient had a complete and uncomplicated recovery. Listeria meningitis is a rare presentation in immunocompetent children, but should be considered in the setting of diarrhea, failure to respond to cephalosporin therapy, or suspected immunodeficiency.

Imported childhood malaria: the Dublin experience, 1999-2006.

AIMS: Imported childhood malaria has never been studied in Ireland. We aimed to document the incidence and species of malaria in children presenting to paediatric hospitals in Dublin and to examine management and outcome measures. METHODS: Subjects were identified through laboratory archives from the three paediatric hospitals in Dublin. Clinical data were extracted retrospectively from clinical and laboratory records. RESULTS: As much as 67 episodes of malaria occurred in 66 children. Episodes occurred among new immigrants (n = 31) and Irish residents (n = 33) who travelled to endemic regions. The majority of those who travelled to endemic regions did not receive appropriate prophylaxis. Plasmodium falciparum was identified in 64 (95%) episodes, 26 with a parasite load above 2%. Eighteen children developed complications. All cases were treated successfully. CONCLUSIONS: Irish health-care practitioners need to encourage malaria prophylaxis among travellers to malaria-endemic regions. Management guidelines should be formulated to assist Irish clinicians treating this potentially fatal illness.

Haemoglobinopathy screening in an maternity hospital.

Recent changes in population movement mean that an increasing number of mothers who deliver in Ireland and their infants are at risk of haemoglobinopathies, in particular sickle cell anaemia. Early detection of sickle cell anaemia improves outcome. For this reason, many hospitals have established antenatal and neonatal screening programmes targeting high-risk ethnic groups. We audited the provision rate of one such programme operated in the National Maternity Hospital in 2003. Using the hospital's databases, we estimated the number of mothers from high-risk ethnic groups, and how many were appropriately screened. We then calculated the neonatal screening provision rate to those infants at risk of homozygous haemoglobinopathies. In 2003, 1231 (14.9%) women from high-risk ethnic groups delivered in the National Maternity Hospital. Nine hundred and ninety one (80.5%) were screened appropriately. One hundred and thirty of these women had abnormal antenatal screens, resulting in 131 infants delivered at risk of homozygous haemoglobinopathy. Fifty eight of these infants (45%) were screened in the neonatal period. The screening programme audited did not achieve a satisfactory provision rate either antenatally or neonatally.