Infantile-onset Pompe disease: A case series highlighting early clinical features, spectrum of disease severity and treatment response.

AIM: Pompe disease is a rare, autosomal, recessive disorder. Alterations in the gene encoding lysosomal acid alpha-glucosidase cause impaired glycogen degradation and resultant lysosomal glycogen accumulation. Classic infantile-onset Pompe disease (IPD) manifests soon after birth, severe cases have complete/near complete enzyme deficiency. IPD is associated with a broad spectrum of non-specific clinical features, and diagnostic delays are common. Without treatment, death typically occurs within the first 2 years of life. We present case experiences to help expand paediatricians' understanding of factors contributing to diagnostic delay, clinical decline and to highlight the need for timely therapy. METHODS: Data were extracted from IPD cases managed at our hospital. Key aspects of clinical presentation, diagnosis, genetic variations, management and overall outcomes were collated then compared with what is already known in the literature. RESULTS: We report four IPD cases (three female). Two patients were cross-reactive immunological material negative. Age at symptom onset was 3-9 months, presenting clinical features were varied, and confirmatory diagnosis was significantly delayed in one patient. In concert with the literature, cardiomegaly, ventricular hypertrophy and delayed developmental milestones were seen in all four cases. Our cases demonstrate a range of disease severity, response to enzyme replacement therapy and antibody development. Significant immune responses were seen in two cases (one cross-reactive immunological material positive); despite immunomodulation therapy, both were associated with fatal outcomes. CONCLUSION: Timely diagnosis and initiation of enzyme replacement therapy is critical to patient outcomes as IPD progresses rapidly and irreversible changes in clinical status may occur during the delay.

Do they stay, or do they go? Children presenting to five emergency departments across New South Wales, Australia with acute burn injuries: a retrospective review.

OBJECTIVE: The overall objective of the study was to describe the disposition status of children presenting with a burn injury to five emergency departments (ED) across New South Wales (NSW), Australia. DESIGN: A retrospective study design was used to review routinely collected ED data. SETTING: Study sites included five acute hospitals across NSW, Australia. PARTICIPANTS: During the 5-year study period between 1 January 2015 to 31 December 2020, there were 5213 paediatric burn injury presentations. RESULTS: The mean age of burn injury presentations was 24 months (Inter-Quartile-Range (IQR) 12-84), of which 57% (2951/5213) were males. The most common presentation time was between 16:00 and 23:59 hours (63%, 3297/5213), and the median time spent in the ED was 3 hours (IQR 1-4). The majority (80%, 4196/5213) of the burn injuries presentations did not require hospital admission. The most common principal diagnoses were 'Burn body region unspecified' (n=1916) and 'Burn of wrist and hand' (n=1060). CONCLUSION: Most children who presented to the hospital with a burn injury were not admitted. Often the details of these burns were poorly recorded and a complete picture of the true burden of burn injury in children, especially the ongoing care given outside the acute hospital setting, is missing. This information is crucial, as it would inform future models of care as the paradigm shifts rapidly towards primary, ambulatory and outpatient models of care.

Rare Case of Hepatic Gaucheroma in a Child on Enzyme Replacement Therapy.

BACKGROUND: We present a 6 year old boy with type I Gaucher treated from 16 months with ERT, developing focal Gaucheroma in the liver at 3.5 years. CASE: The subject presented at 13 months of age with anaemia, thrombocytopenia and hepatosplenomegaly. Gaucher disease was confirmed by leucocyte enzyme assay. A homozygous change: c.1193G>A (p.Arg398Gln) in the GBA gene was identified. He had normal neurology with normal saccades. Imiglucerase was administered at 60 IU/kg/fortnight from 15 months as per Australian regulations with good clinical response. At 3.5 years hepatic ultrasound demonstrated a nodular cystic lesion measuring 7 × 5.3 × 5.1 cm in the right lobe of liver, confirmed on MRI. Biopsy demonstrated acellular hyaline necrosis, portal-portal bridging fibrosis and nodules of Gaucher cells. Cystic fluid comprised necrotic debris and Gaucher cells. Further evaluation over 18 months including repeat MRI, biopsy, alpha-fetoprotein monitoring and whole-body FDG-Pet scan demonstrate no malignancy. CONCLUSION: GD is the most common lysosomal storage disorder. The aetiology, natural history and optimal management strategy of rare Gaucheroma in paediatric cases has not been defined particularly in regards to malignancy risk.

Safety and Efficacy of Elosulfase Alfa in Australian Patients with Morquio a Syndrome: A Phase 3b Study

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.