Background Fabry Disease (FD) is a rare X-linked metabolic lysosomal disorder. FD has a broad range of symptoms which vary markedly between patients. The heterogenous nature of the disease makes diagnosis difficult for health care professionals (HCPs), which in turn has a significant effect on the patient’s quality of life (QoL). As few adolescent patients are eligible for treatment, to date there has been little published data on the burden of disease and impact of treatment on these patients and their caregivers. This study was developed to provide some insight into these groups. Methods An online-based survey was performed to gather further insights on the burden of FD in 14 adolescents aged 12–15 years old across three European countries, from the perspective of the patients, caregivers and HCPs. Results Symptom burden was found to be high in the adolescent population, with ‘pain’ and ‘intolerance to heat or cold’ commonly reported symptoms, both by patients and to HCPs. Eleven of the 14 patients surveyed were receiving enzyme replacement therapy (ERT), with their post-ERT symptomology showing improvement when compared to symptoms before receiving ERT. The majority of caregivers believe their child’s overall health has improved since starting ERT. While there was a positive outlook towards ERT noted by the patients and caregivers, 4/5 HCPs believed there is ‘a need for more efficacious treatment options’ and all HCPs noted that there is ‘a need for more manageable treatment options’. FD was shown to place a burden on caregivers, who reported feelings of guilt and absences from work. Conclusions Data show there is a significant symptom burden for the adolescent, which affects their QoL and mental health, as well as placing a burden on the wider family. While ERT is an effective treatment and provides symptom relief for many of the respondents in the survey, they still reported symptom burden. Additionally, there was reporting of reluctance to engage in treatment or difficulties associated with the treatment. Heterogeneity in symptom presentation suggests that the treatment regimen needs to be tailored to the individual. Physicians therefore need to have a choice of treatment options available to help them manage symptoms and disease where the benefit to risk ratio is in favour of undergoing treatment.

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AimsBackground Neonatal Hyperammonemia is a medical emergency requiring prompt management. The combination of neonatal hyperammonemia, lactic acidosis, ketonuria, and hypoglycemia is pathognomonic for carbonic anhydrase VA (CA-VA) deficiency (figure 1). Methods Objectives To present two siblings with CA-VA deficiency of East Asian ancestry and their clinical course. ResultsClinical cases Parents are non-consanguineous from Punjab, India. The first patient is a full-term male who presented with hyperammonemic crisis on the second day of life. The highest ammonia level was 361umol/L (15-55). His metabolic investigations (plasma amino acids, acylcarnitine profile, and urine organic acids) had some overlapping features with a urea cycle disorder and organic acidemia. He was treated initially with nitrogen scavenger therapy and Carglumic acid but eventually needed hemodialysis. DNA analysis on an NGS Urea cycle panel identified two heterozygous variants in CA-VA: c.721G>A, p.Glu241Lys and c.619-?_774+?del. Both variants were considered probably pathogenic. Parental studies showed trans configuration. This confirmed the diagnosis of CA-VA deficiency (JIMD Reports 2020: 1-6). His sibling, also a fullterm male, was diagnosed antenatally with CA-VA deficiency based on molecular studies on amniocentesis. He was managed proactively for potential hyperammonemia at birth with IV fluids 10% Dextrose, intralipid 2 gm/kg, and Carbaglu 100 mg/kg BID. The urine organic acids were completely normal. He did not require any further interventions. He was given regular formula and discharged on day five. Currently, the older brother is two years old and the younger brother is 11 months. Neither of them have had any further crisis and both are doing well without any treatment.

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