Health-related out-of-pocket expenses for children living with rare diseases - tuberous sclerosis and mitochondrial disorders: A prospective pilot study in Australian families.

AIM: We aimed to describe health-related out-of-pocket (OOP) expenses incurred by Australian families living with children with chronic and complex diseases. METHODS: A prospective pilot study of OOP expenses in families with children with tuberous sclerosis (TS) or mitochondrial disorders (MD) in 2016-2017. An initial survey assessed the family's financial situation, child's health functioning and estimated previous 6 months' and lifetime OOP expenses. Thereafter, families completed a survey each month for 6 months, prospectively tracking OOP expenses. RESULTS: Initial surveys were completed by 13 families with 15 children; median age 7 years (range: 1-12); 5 with MD, 10 with TS. All families reported OOP expenses: 38% paid $2000 per annum, more than double the annual per-capita OOP costs reported for Australia by the Organisation for Economic Co-operation and Development. Eight families estimated $5000-$25 000 in OOP expenses over their child's lifetime and 62% of mothers reduced or stopped work due to caring responsibilities. Eleven families paid annual private health insurance premiums of $2000-$5122, but 72% said this was poor value-for-money. Prospective tracking by eight families (9 children) identified the median OOP expenditure was $863 (range $55-$1398) per family for 6 months. OOP spending was associated with visits to allied health professionals, non-prescription medicines, special foods, supplements and disposable items. Eight families paid for 91 prescription medications over 6 months. CONCLUSION: All families caring for children with TS or MD reported OOP expenses. A larger study is needed to explore the affordability of health care for children living with a broader range of chronic diseases.

Australian children living with rare diseases: health service use and barriers to accessing care.

BACKGROUND: Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare. We aimed to determine health service utilization by Australian children with rare diseases and barriers to accessing healthcare. METHODS: Parents completed an online survey on health professional and emergency department (ED) presentations, hospitalization, and barriers to accessing services. Potential barriers to service access included residential location (city, regional, remote) and child health-related functioning, determined using a validated, parent-completed measure-of-function tool. RESULTS: Parents of 462 children with over 240 rare diseases completed the survey. Compared with the general population, these children were more likely to be hospitalized [odds ratio (OR) = 17.25, 95% confidence interval (CI) = 15.50-19.20] and present to the ED (OR = 4.15, 95% CI = 3.68-4.68) or a family physician (OR = 4.14, 95% CI = 3.72-4.60). Child functional impairment was nil/mild (31%), moderate (48%) or severe (22%). Compared to children with nil/mild impairment, those with severe impairment were more likely to be hospitalized (OR = 13.39, 95% CI = 7.65-23.44) and present to the ED (OR = 11.16, 95% CI = 6.46-19.27). Most children (75%) lived in major cities, but children from regional (OR = 2.78, 95% CI = 1.72-4.55) and remote areas (OR = 9.09, 95% CI = 3.03-25.00) experienced significantly more barriers to healthcare access than children from major cities. Barriers included distance to travel, out-of-pocket costs, and lack of specialist medical and other health services. CONCLUSIONS: Children with rare diseases, especially those with severe functional impairment have an enormous impact on health services, and better integrated multidisciplinary services with patient-centered care are needed. Access must be improved for children living in rural and remote settings.

Treatment of HMG-CoA Lyase Deficiency-Longitudinal Data on Clinical and Nutritional Management of 10 Australian Cases.

3-Hydroxy-3-Methylglutaryl-CoA Lyase (HMGCL) deficiency can be a very severe disorder that typically presents with acute metabolic decompensation with features of hypoketotic hypoglycemia, hyperammonemia, and metabolic acidosis. A retrospective chart and literature review of Australian patients over their lifespan, incorporating acute and long-term dietary management, was performed. Data from 10 patients contributed to this study. The index case of this disorder was lost to follow-up, but there is 100% survival in the remainder of the cases despite several having experienced life-threatening episodes. In the acute setting, five of nine patients have used 900 mg/kg/day of sodium D,L 3-hydroxybutyrate in combination with intravenous dextrose-containing fluids (delivering glucose above estimated basal utilization requirements). All patients have been on long-term protein restriction, and those diagnosed more recently have had additional fat restriction. Most patients take L-carnitine. Three children and none of the adults take nocturnal uncooked cornstarch. Of the cohort, there were two patients that presented atypically-one with fulminant liver failure and the other with isolated developmental delay. Dietary management in patients with HMGCL deficiency is well tolerated, and rapid institution of acute supportive metabolic treatment is imperative to optimizing survival and improve outcomes in this disorder.

Diagnosis and management of children with McArdle Syndrome (GSD V) in New South Wales.

Glycogen storage type V (GSD V-McArdle Syndrome) is a rare neuromuscular disorder characterised by severe pain early after the onset of physical activity. A recent series indicated a diagnostic delay of 29 years; hence reports of children affected by the disorder are uncommon (Lucia et al., 2021, Neuromuscul Disord, 31, 1296-1310). This paper presents eight patients with a median onset age of 5.5 years and diagnosis of 9.5 years. Six patients had episodes of rhabdomyolysis with creatine kinase elevations >50 000 IU/L. Most episodes occurred in relation to eccentric non-predicted activities rather than regular exercise. One of the patients performed a non-ischaemic forearm test. One patient was diagnosed subsequent to a skeletal muscle biopsy, and all had confirmatory molecular genetic diagnosis. Three were homozygous for the common PYGM:c.148C > T (p.Arg50*) variant. All but one patient had truncating variants. All patients were managed with structured exercise testing to help them identify 'second-wind', and plan an exercise regimen. In addition all also had an exercise test with 25 g maltodextrin which had statistically significant effect on ameliorating ratings of perceived exertion. GSD V is under-recognised in paediatric practice. Genetic testing can readily diagnose the condition. Careful identification of second-wind symptomatology during exercise with the assistance of a multi-disciplinary team, allows children to manage activities and tolerate exercise. Maltodextrin can be used for structured exercise, but excessive utilisation may lead to weight gain. Early intervention and education may improve outcomes into adult life.

Liver transplantation in children with inborn errors of metabolism: 30 years experience in NSW, Australia.

BACKGROUND: Inborn errors of metabolism (IEM) are a diverse group of genetic disorders that can result in significant morbidity and sometimes death. Metabolic management can be challenging and burdensome for families. Liver transplantation (LT) is increasingly being considered a treatment option for some IEMs. IEMs are now considered the second most common reason for pediatric LT. AIM: To review the data of all children with an IEM who had LT at The Children's Hospital at Westmead (CHW), NSW, Australia between January 1986 and January 2019. METHODS: Retrospective data collected from the medical records and genetic files included patient demographics, family history, parental consanguinity, method of diagnosis of IEM, hospital and intensive care unit admissions, age at LT, graft type, clinical outcomes and metabolic management pre and post-LT. RESULTS: Twenty-four LT were performed for 21 patients. IEM diagnoses were MSUD (n = 4), UCD (n = 8), OA (n = 6), TYR type I (n = 2) and GSD Ia (n = 1). Three patients had repeat transplants due to complications. Median age at transplant was 6.21 years (MSUD), 0.87 years (UCD), 1.64 years (OA) and 2.2 years (TYR I). Two patients died peri-operatively early in the series, one died 3 months after successful LT due to septicemia. Eighteen LTs have been performed since 2008 in comparison to six LT prior to 2008. Dietary management was liberalized post LT for all patients. CONCLUSIONS: Referral for LT for IEMs has increased over the last 33 years, with the most referrals in the last 10 years. Early LT has resulted in improved clinical outcomes and patient survival.

The use of sodium DL-3-Hydroxybutyrate in severe acute neuro-metabolic compromise in patients with inherited ketone body synthetic disorders.

BACKGROUND: Ketone bodies form a vital energy source for end organs in a variety of physiological circumstances. At different times, the heart, brain and skeletal muscle in particular can use ketones as a primary substrate. Failure to generate ketones in such circumstances leads to compromised energy delivery, critical end-organ dysfunction and potentially death. There are a range of inborn errors of metabolism (IEM) affecting ketone body production that can present in this way, including disorders of carnitine transport into the mitochondrion, mitochondrial fatty acid oxidation deficiencies (MFAOD) and ketone body synthesis. In situations of acute energy deficit, management of IEM typically entails circumventing the enzyme deficiency with replenishment of energy requirements. Due to profound multi-organ failure it is often difficult to provide optimal enteral therapy in such situations and rescue with sodium DL-3-hydroxybutyrate (S DL-3-OHB) has been attempted in these conditions as documented in this paper. RESULTS: We present 3 cases of metabolic decompensation, one with carnitine-acyl-carnitine translocase deficiency (CACTD) another with 3-hydroxyl, 3-methyl, glutaryl CoA lyase deficiency (HMGCLD) and a third with carnitine palmitoyl transferase II deficiency (CPT2D). All of these disorders are frequently associated with death in circumstance where catastrophic acute metabolic deterioration occurs. Intensive therapy with adjunctive S DL-3OHB led to rapid and sustained recovery in all. Alternative therapies are scarce in these situations. CONCLUSION: S DL-3-OHB has been utilised in multiple acyl co A dehydrogenase deficiency (MADD) in cases with acute neurological and cardiac compromise with long-term data awaiting publication. The use of S DL-3-OHB is novel in non-MADD fat oxidation disorders and contribute to the argument for more widespread use.

Australian children living with rare diseases: experiences of diagnosis and perceived consequences of diagnostic delays.

BACKGROUND: Children and families living with rare disease often experience significant health, psychosocial, economic burdens and diagnostic delays. Experiences appear to be constant, regardless of the specific rare disease diagnosis. Systematically collected Australian data to support policy response on rare diseases are scarce. We address this gap by providing survey results about 462 children aged <19 years living with approximately 200 different rare diseases. RESULTS: Of 462 children, 96% were born in Australia, 55% were male, median age was 8.9 years (0-18.2). Four-hundred-and-twenty-eight (93%) had received a definitive diagnosis but 29 (7%) remained undiagnosed. Before receiving the correct diagnosis 38% consulted ≥ 6 different doctors. Among those with a diagnosis, 37% believed the diagnosis was delayed and 27% initially received a wrong diagnosis. Consequences of delayed diagnosis include anxiety, loss of reproductive confidence because of an ill-defined genetic risk, frustration and stress (54%), disease progression (37%), delays in treatment (25%) and inappropriate treatments (10%). Perceived reasons for diagnostic delays included lack of knowledge about the disease among health professionals (69.2%), lack of symptom awareness by the family (21.2%) and difficulties accessing tests (17.9%). Children with inborn errors of metabolism were less likely to have a delayed diagnosis compared with other disease groups (Chi-Sq = 17.1; P < 0.0001), most likely due to well-established and accessible biochemical screening processes. Diagnosis was given in person in 74% of cases, telephone in 18.5% and via a letter in 3.5%. Some families (16%) were dissatisfied with the way the diagnosis was delivered, citing lack of empathy and lack of information from health professionals. Psychological support at diagnosis was provided to 47.5%, but 86.2% believed that it should always be provided. Although 74.9% of parents believed that the diagnosis could have an impact on future family planning, only 44.8% received genetic counselling. CONCLUSION: Parents of children living with rare chronic and complex diseases have called for better education, resourcing of health professionals to prevent avoidable diagnostic delays, and to facilitate access to early interventions and treatments. Access to psychological support and genetic counselling should be available to all parents receiving a life-changing diagnosis for their child.

The first eighteen months of a paediatric ambulatory and community service.

Hospital admission is distressing and traumatic for children as they are separated from their families and home. Internationally, and in Australia, alternative models of health care are being developed to meet the needs of children and their families. We describe the first eighteen months of the establishment of a paediatric ambulatory and community service in a district health service in New South Wales. Key outcomes include: increased referral to the service from acute hospital and primary care services; parental satisfaction and saved hospital bed-days. Lessons learnt in the setting up of this service include the need for proactive engagement of consumers and stakeholders; clear definition of roles and responsibilities; and measurable and reasonable performance indicators.