Parental experiences of raising a child with medium chain Acyl-CoA Dehydrogenase deficiency

Newborn screening enabling early diagnosis of medium chain acyl-CoA dehydrogenase deficiency (MCADD) has dramatically improved health outcomes in children with MCADD. Achieving those outcomes depends on effective management by parents. Understanding parental management strategies and associated anxieties and concerns is needed to inform provision of appropriate care and support. Semi structured interviews were conducted with a purposive sample of parents of children aged two to twelve years. Thematic analysis identified two main themes. Managing dietary intake examined how parents managed day-to-day dietary intake to ensure adequate intake and protection of safe fasting intervals. Managing and preventing illness events explored parental experiences of managing illness events and their approach to preventing these events. Management strategies were characterised by caution and vigilance and influenced by a lack of confidence in others to manage the condition. The study identifies the need for increased awareness of the condition, particularly in relation to emergency treatment

What are the information needs of parents caring for a child with Glutaric aciduria type 1?

BACKGROUND: Newborn screening has enabled the early diagnosis of Glutaric aciduria type 1, with the possibility of improving neurological outcomes in affected children. Achieving those outcomes requires parents to effectively manage their child's condition by adherence to a strict dietary regime and responding to situations that may trigger decompensation. The specific information and support needs of this group of parents are unknown. METHODS: A focus group with five parents was conducted to gain insights into the information that parents needed and the ways in which they accessed and used information to manage their child's condition. A topic guide was used to direct the discussion which was recorded and fully transcribed. All participants gave informed consent. Data were analysed using thematic analysis, a structured approach that contributes to transparency and validity of results while allowing the integration of predetermined and emerging themes. To ensure rigour, two researchers were involved in initial coding of data and key analytic decisions. RESULTS: Two main themes were identified. 'Understanding the condition' explored parent's needs to understand the scientific complexity of the condition and to be aware of the worst case scenario associated with loss of metabolic control. 'Managing the condition' explained how parents co-ordinated and controlled the involvement of other carers and parents' need to be active partners in medical management to feel in control of the situation. CONCLUSIONS: The study highlights the importance of addressing parents' initial and ongoing informational needs so they can fulfil their role and protect their child from metabolic harm

“It’s Just Always Eating”: The Experiences of Young People Growing up Medium Chain Acyl-coA Dehydrogenase Deficiency

Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare metabolic disorder, and commonly now part of newborn screening programs. Those diagnosed at birth are now progressing from childhood to adulthood. The study aim was to explore young people’s experiences of living with MCADD and managing their condition. A descriptive qualitative study design involving semi-structured interviews with 12 participants aged 10 to 15 years, recruited from one regional pediatric metabolic disorder service in England. Data were analyzed using thematic analysis. The two major themes were “Eating for energy” and “Growing into a self-management role.” Self-monitoring and self-management skills had been nurtured from early childhood by parents and healthcare providers. Young people’s anxieties concerned having to maintain adequate energy input to stay safe and the associated burden of responsibility. Growing up with MCADD presents specific challenges. Self-management and ongoing support are important for dealing with those challenges

“It’s Just Always Eating”: The Experiences of Young People Growing up Medium Chain Acyl-coA Dehydrogenase Deficiency

Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare metabolic disorder, and commonly now part of newborn screening programs. Those diagnosed at birth are now progressing from childhood to adulthood. The study aim was to explore young people’s experiences of living with MCADD and managing their condition. A descriptive qualitative study design involving semi-structured interviews with 12 participants aged 10 to 15 years, recruited from one regional pediatric metabolic disorder service in England. Data were analyzed using thematic analysis. The two major themes were “Eating for energy” and “Growing into a self-management role.” Self-monitoring and self-management skills had been nurtured from early childhood by parents and healthcare providers. Young people’s anxieties concerned having to maintain adequate energy input to stay safe and the associated burden of responsibility. Growing up with MCADD presents specific challenges. Self-management and ongoing support are important for dealing with those challenges

Cerebral venous sinus thrombosis in homocystinuria: Dietary intervention in conjunction with anticoagulation

The presentation of cerebral venous sinus thrombosis may be acute or chronic with a progressive clinical course. The diagnosis can be challenging, and there are several clinical syndromes associated with the disease. It is also an uncommon but recognised complication of homocystinuria. We describe a case where early anticoagulation, together with dietary intervention, was associated with a favourable clinical outcome

N-carbamoylglutamate-responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects

9 páginas, 3 figurasN-carbamoyl-l-glutamate (NCG), the N-acetyl-l-glutamate analogue used to treat N-acetylglutamate synthase deficiency, has been proposed as potential therapy of carbamoyl phosphate synthetase 1 deficiency (CPS1D). Previous findings in five CPS1D patients suggest that NCG-responsiveness could be mutation-specific. We report on a patient with CPS1D, homozygous for the novel p.(Pro1211Arg) CPS1 mutation, who presented at 9 days of life with hyperammonemic coma which was successfully treated with emergency measures. He remained metabolically stable on merely oral NCG, arginine, and modest protein restriction. Ammonia scavengers were only added after poor dietary compliance following solid food intake at age 1 year. The patient received a liver transplantation at 3.9 years of age, having normal cognitive, motor, and quality of life scores despite repeated but successfully treated episodes of hyperammonemia. Studies using recombinantly produced mutant CPS1 confirmed the partial nature of the CPS1D triggered by the p.(Pro1211Arg) mutation. This mutation decreased the solubility and yield of CPS1 as expected for increased tendency to misfold, and reduced the thermal stability, maximum specific activity (V max; ~2-fold reduction), and apparent affinity (~5-fold reduction) for ATP of the purified enzyme. By increasing the saturation of the NAG site in vivo, NCG could stabilize CPS1 and minimize the decrease in the effective affinity of the enzyme for ATP. These observations, together with prior experience, support the ascertainment of clinical responsiveness to NCG in CPS1 deficient patients, particularly when decreased stability or lowered affinity for NAG of the mutant enzyme are suspected or proven.Grants to V.R. from the Fundación Inocente Inocente2018 (Spain) and BFU2017-84264-P of MINECO-SpanishGovernment. N.G. and B.B. had contracts from CIBERER-ISCIII and Fundación Inocente Inocente. Orphan Europefunded editorial assistance.Peer reviewe

Intron retention is among six unreported AGL mutations identified in Malaysian GSD III patients

Background: Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown. Objective: The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population. Methods: A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan® SNP Genotyping assay. Results: We identified six unreported mutations (c.1423+1G>T, c.2914_2915delAA, c.3814_3815delAG, c.4333T>G, c.4490G>A, c.4531_4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%). Conclusion: The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested. © 2019, The Genetics Society of Korea