Palliative Care in Children with Inherited Metabolic Diseases: Why does it matter?

BACKGROUND: Inherited metabolic diseases (IMD) bring considerable burden on the child and family. Challenging areas for health care include the identification of distressing symptoms, prognostic uncertainty, and bereavement. Literature regarding the impact of paediatric palliative care (PPC) is scarce. OBJECTIVE: This study aims to evaluate children with IMD referred to a PPC team (PPCT) and to analyse its impact on home care, decision to limit treatment (DLT), use of hospital resources (emergency department admissions - EDA, hospital admissions - HA, intensive care admissions - ICA) and end of life support. METHODS: Retrospective cohort study of children with IMD referred to a specialized PPCT (2016-2022). We assessed clinical data: symptoms control, time of referral and length of the follow-up period, DLT, device dependency, use of hospital resources prior to and after referral, place of death and end-of-life support. RESULTS: Fifteen children with IMD were referred to PPCT (8% of total referrals), with median age of 7 years (4 months - 17 years); 53% female. All children were non or pre-verbal. Most prevalent symptoms were neurologic and motor impairment (100%), respiratory and gastrointestinal (75%). 80% had tube feeding, 90% had some respiratory device (non-invasive ventilation in 23%). All children had multidrug use, with a mean of 6 drugs per child (2-9). 73% had home PPC and 80% had DLT planned. Nine children died (78% in hospital), after a mean of 17 months of follow-up (2 months to 4 years), all with DLT planned. 67% had support from PPCT at the end of life. All these families received emotional support. Decrease in EDA (10 vs 2) was noticed before and after PPCT. No impact was seen in HA and ICA (6 vs 5 and 1 vs 1, respectively) and there was a longer mean of hospitalisation stay (15 vs 32 days). CONCLUSION: Our cohort includes a group of children with severe, complex and neurodegenerative IMD. They need multiple medications for symptoms control, are highly dependent on medical devices and consume significant healthcare resources. Communication impairment adds complexity being a major barrier to symptom assessment. PPCT referral allowed home support, anticipated care plans development with end of life and bereavement support, as well as a tendency towards a reduction in EDA. These findings reinforce the need for holistic approach to identify and address the PPC needs of children with IMD.

Combined Oxidative Phosphorylation Deficiency Type-13 with Perinatal Presentation: A Case Report.

INTRODUCTION: Polynucleotide phosphorylase is involved in RNA processing in mitochondria. Biallelic variants in PNPT1 cause mitochondrial RNA import protein deficiency and heterogeneous clinical manifestations. CASE REPORT: The patiest was the first child of remote consanguineous parents, born at 35 weeks by caesarean section due to fetal growth restriction. Apgar index was 9/10/10. Birth weight, length and head circumference were at 3rd, <3rd and 10th percentiles, respectively. In the first hours of life, respiratory distress, hypoglycaemia and seizures ensued. She started invasive mechanic ventilation, phenobarbital and was transferred to ICU. Physical examination showed minor facial dysmorphisms, brief eye-opening, hypotonia and hyporeflexia. Electroencephalogram showed immature pattern and multifocal paroxysmal activity. MRI at D8 of life showed severe reduced brain volume. Normal aminoacid screen was also observed. Expanded newborn screening was negative. Mitochondrial organic aciduria was seen. WES showed a homozygotic likely pathogenic variant in the PNPT1 gene. MRI at 6-months showed brain atrophy, thin corpus callosum, reduced brainstem volume. Bilateral and symmetrical lesions in globi pallidi, compatible with Leigh síndrome were observed. Currently, at 14 months, no neurodevelopment progress, dystonia, visual deficit, sensorineural deafness, hypertrophic cardiomyopathy and microcephaly are observed. CONCLUSION: The early and severe Leigh-like presentation of our patient expands the phenotype spectrum of this disease. As far as we know, this is the first reported case of PNPT1 mutation with onset in the perinatal period. Moreover, hypertrophic cardiomyopathy has not yet been described in association with mutation of the PNPT1 gene. WES was the key for early diagnosis in this patient. It should be done in all children with severe clinical presentation of unknown origin.

The needs of children receiving end of life care and the impact of a paediatric palliative care team: a retrospective cohort study.

Published data collected in hospital during the last year of life of children with life-limiting complex chronic conditions (CCC) is scarce, yet critical, for the implementation of paediatric palliative care (PPC). This study aims to describe the last year of life of children with CCC, in terms of clinical characteristics, hospital resources and the impact of referral to a hospital-based PPC team (PPCT). Using a retrospective cohort study, we examined the clinical records of children aged 1-18 years of age with CCC who died in a tertiary hospital between January 2016 and December 2020. Hospital resources utilised in the last year of life, therapies and procedures during the final week of life, decision to limit treatment (DLT), referral to the PPCT and place of death were analysed. Seventy-two patients (60% male) with a median age of 10.1 years were included. Most had ≥ 2 CCC (58%) with cancer as the most common diagnosis (47%). The group with ≥ 3 CCC (n = 23) had longer hospital stays (p = 0.041). Of the 17 patients referred to the PPCT, there was a higher frequency of DLT (94% vs. 40% in non-referred, p < 0.001), greater use of subcutaneous route (53% vs. 0%, p < 0.001), lower frequency of blood transfusions (12% vs. 55%, p = 0.002) and a lower proportion of deaths in the Intensive Care Unit (6% vs. 64%, p < 0.001). CONCLUSIONS: Early implementation of PPC optimises the use of hospital resources, minimises invasive procedures and therapies, and may develop effective and sustainable alternatives which are better suited to the needs of children and families. WHAT IS KNOWN: • In recent years, there has been an increased prevalence of complex chronic condition (CCC), which has led to more specialised and prolonged medical care until the end of life. • There are few paediatric studies on use of hospital resources and the invasiveness of procedures in the last year of life for children. WHAT IS NEW: • This study is one of the few to provide a comprehensive characterisation of the last year of life of children/adolescents with CCC. • Timely referral to a specialised PPC team optimises the use of hospital resources, minimise invasive procedures and develop effective and sustainable alternatives which are better suited to the needs of children and/or families.

Trisomy 18-when the diagnosis is compatible with life.

Trisomy 18 is an autosomal chromosomal disorder characterized by the presence of an extra 18 chromosome. In the last decades, and as novel therapeutic options emerged, a paradigm shift on the treatments available to these children occurred, establishing the need to deepen the knowledge regarding the management/treatment of children diagnosed with trisomy 18. This retrospective cohort study sought to characterize the clinical path and survival of the children with the diagnosis of trisomy 18 followed in a tertiary pediatric hospital between 1995 and 2020. Medical records were reviewed, and epidemiological and clinical features and follow-up data were collected. Six patients were identified, two with mosaicism (33.3%) and four were female (66.7%). All had cardiovascular, cognitive, and physical development anomalies or minor congenital anomalies. Most presented neurological anomalies (n = 4, 66.7%) and feeding difficulties (n = 4, 66.7%). Four children (66.7%) required medical devices or equipment and all required chronic medication. Two children (33.3%) underwent surgical interventions. Four children (66.7%) were hospitalized in the last year of life. Three patients had a do not resuscitate order (50%) but only one child was referred to a pediatric palliative care team (16.7%). One-month, 1-year, and 10-year survival were 66.7% (n = 4), 33.3% (n = 2, both with mosaicism), and 16.7% (n = 1, with mosaicism) respectively. CONCLUSIONS: Knowledge of the multiple comorbidities and complex care needs of children with this syndrome is crucial. Every-day care and decisions about invasive treatments may raise ethical issues. Early referral to pediatric palliative care teams is essential to promote a holistic advanced care plan for both the patient and his family. WHAT IS KNOWN: • The increase in survival and the high morbimortality that trisomy 18 still entails demands a careful deliberation on the use of invasive treatment. WHAT IS NEW: • Recent studies show that the labels of "incompatible with life"/"lethal" are not adequate, establishing a need to change this mindset. • The development of pediatric palliative care teams in the last decade and early referral allow for an optimal individualized advanced care plan. Under-referral to pediatric palliative care teams persists and efforts must be made to increase awareness of their existence and role in patient care.

Spinal cord ischaemic injury while playing in a playground.

Spinal cord ischaemia is a rare condition in children in which imaging diagnosis can be difficult and treatment guidelines are not well established. We describe a case of a previously healthy 13-year-old girl admitted to the emergency department with an acute flaccid paralysis of the lower limbs, abdominal and dorsal pain, and bladder dysfunction. A few hours earlier, she had been playing on a swing with hyperextension and an arched back position. Spinal cord MRI was normal in the first hours, but ischaemic signs were described in a second examination performed some hours later. We discuss the extensive investigation for differential diagnosis and the management of this case.

[Hospital Inpatient Use in Mainland Portugal by Children with Complex Chronic Conditions (2011 - 2015)]. / Utilização do Internamento Hospitalar em Portugal Continental por Crianças com Doenças Crónicas Complexas (2011 ­ 2015).

INTRODUCTION: Due to epidemiological change, interest in complex chronic conditions has been increasing within the pediatric health system. As such, we aim to evaluate hospital inpatient care in the National Health Service (mainland Portugal) by pediatric patients (0 - 17 years) with complex chronic conditions. MATERIAL AND METHODS: Observational longitudinal retrospective epidemiological study using anonymized administrative data. We selected hospitalizations within the pediatric age limit, 2011 - 2015; healthy newborns and radiotherapy outpatients were excluded. A descriptive analysis of the admissions with complex chronic conditions was analysed by number of complex chronic conditions categories and by complex chronic conditions categories. Non-parametric tests were applied to length of stay, expense, and mortality. RESULTS: Out of 419 927 admissions, 64 918 (15.5%) contained at least one complex chronic conditions code. These admissions due to complex chronic conditions represented 29.8% of hospital days, 39.4% of expense and 87.2% of deaths. Compared to those without complex chronic conditions, expense was double (median €1467 vs €745) and mortality 40 times higher (2.4% vs 0.06%). Of these, 46% were planned (no complex chronic conditions 23.2%); 64.8% occurred in group III - IV hospitals (no complex chronic conditions 27.1%). Malignant was the most frequent category (23.0%); neonatal had the highest median length of stay (12 days, 6 - 41), median expense (€3568,929 - 24 602), and number of deaths (43.5% of total). DISCUSSION: As in other developed countries where the number of pediatric admissions is decreasing, in mainland Portugal we found an increase in the proportion of complex chronic conditions admissions, which are longer, costlier and deadlier (trends intensified in the presence of two or more complex chronic conditions categories). CONCLUSION: Complex chronic conditions are relevant in the activity and costs regarding pediatric hospitalizations in mainland Portugal. Recognizing this and integrating pediatric palliative care from the moment of diagnosis are essential to promote appropriate hospital use, through the development of effective and sustainable alternatives that meet the needs of children, families, and healthcare professionals.

Introdução: Fruto da mudança epidemiológica, o interesse pelas doenças crónicas complexas no sistema de saúde pediátrico tem vindo a crescer. Assim, pretendemos avaliar a utilização do internamento hospitalar do Serviço Nacional de Saúde (Portugal Continental) por doentes pediátricos (0 ­ 17 anos) com doenças crónicas complexas. Material e Métodos: Estudo epidemiológico observacional longitudinal retrospetivo (base de dados de morbilidade hospitalar anonimizada). Selecionámos episódios de internamento de doentes pediátricos, entre 2011 ­ 2015; excluímos recém-nascidos saudáveis e radioterapia ambulatória. Análise descritiva dos episódios de internamento de doentes pediátricos com doenças crónicas complexas, caracterizados por número e categoria de doenças crónicas complexas. Foram aplicados testes não paramétricos à duração de internamento, despesa e mortalidade. Resultados: Nos 419 927 episódios, constavam códigos de doenças crónicas complexas em 64 918 (15,5%). Estes episódios com doenças crónicas complexas representaram 29,8% dos dias de internamento, 39,4% da despesa e 87,2% dos óbitos. Custaram o dobro dos episódios sem doenças crónicas complexas (€1467 vs €745) e tiveram uma mortalidade 40 vezes superior (2,4% vs 0,06%). Do total, 46,0% foram programados (sem doenças crónicas complexas 23,2%); 64,8% ocorreram em hospitais grupo III ­ IV (sem doenças crónicas complexas 27,1%). Nos episódios com doenças crónicas complexas, a doença maligna foi a categoria mais frequente (23,0%); a maior demora mediana (12 dias, 6 ­ 41), despesa mediana (€3568,929 ­ 24 602) e mortalidade (13,4%) verificaram-se na categoria neonatais. Discussão: Esta análise mostrou que, embora o número absoluto de internamentos de doentes pediátricos esteja a diminuir em Portugal Continental, à semelhança de outros países desenvolvidos, os internamentos com doenças crónicas complexas têm vindo a aumentar proporcionalmente, sendo mais prolongados, onerosos e com maior probabilidade de morte do que os episódios sem doenças crónicas complexas (tendências acentuadas quando constam duas ou mais doenças crónicas complexas). Conclusão: As doenças crónicas complexas são relevantes na atividade e despesa do internamento hospitalar pediátrico em Portugal Continental. Este reconhecimento e a integração de cuidados paliativos pediátricos desde o diagnóstico são essenciais para adequar a utilização do hospital, desenvolvendo alternativas efetivas e sustentáveis que vão ao encontro das necessidades das crianças, famílias e profissionais.

Phenotyping GABA transaminase deficiency: a case description and literature review.

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family.

WITHDRAWN: Long-term ventilation in children: Ten years later.

This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.03.017. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Renal abscesses in childhood: report of two uncommon cases.

Renal abscesses are rare conditions in children, but they must be remembered in differential diagnosis of fever and abdominal pain. The authors report two paediatric cases with unusual presentation. Case 1: a 15-year-old girl was admitted following a period of fever, vomiting and left hypochondrium pain which became more localised to the left lower ribs. Blood tests suggested bacterial infection, but urinalysis and culture were negative. Renal CT scan presented features of bilateral pyelonephritis and left renal abscesses, while ultrasound remained normal until the ninth day of disease. Case 2: a 2-year-old girl, with diagnosis of ß-thalassemia minor, had intermittent diffuse abdominal pain with 2 weeks of evolution. Renal ultrasonography and CT scan showed a heterogeneous mass compatible with Willms tumour. Intraoperative diagnosis was compatible with renal abscess with isolation of Proteus mirabilis in the fluid. Both responded well to long-term antibiotics and to surgical drainage (in the second case).

An 11-year-old boy with pharyngitis and cough: Lemierre syndrome.

The authors present the case of an 11-year-old boy with pharyngitis, treated with amoxicillin, that worsened on day 7, with cough, high fever and refusal to eat. Lethargy and respiratory distress were noted. Based on radiographic findings of bilateral infiltrates he was diagnosed with pneumonia and started on intravenous ampicillin and erythromycin. Two days later he complained of right-sided neck pain and a palpable mass was identified. An ultrasound showed partial thrombosis of the right internal jugular vein and a lung CT scan revealed multiple septic embolic lesions. Lemierre syndrome was diagnosed, antibiotic treatment adjusted and anticoagulation started. A neck CT-scan showed a large parapharyngeal abscess. His clinical condition improved gradually and after 3 weeks of intravenous antibiotics he was discharged home on oral treatment. This case illustrates the importance of diagnosing Lemierre syndrome in the presence of pharyngitis with localised neck pain and respiratory distress, to prevent potentially fatal complications.