Health Care for Mitochondrial Disorders in Canada: A Survey of Physicians

Background: An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care. Methods: We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities. Results: We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend mitochondrial cocktails for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority. Conclusions: While Canadian physicians\u27 views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols

Jacobsen syndrome

Jacobsen syndrome is a MCA/MR contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. To date, over 200 cases have been reported. The prevalence has been estimated at 1/100,000 births, with a female/male ratio 2:1. The most common clinical features include pre- and postnatal physical growth retardation, psychomotor retardation, and characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears, low set posteriorly rotated ears). Abnormal platelet function, thrombocytopenia or pancytopenia are usually present at birth. Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Ocular, hearing, immunological and hormonal problems may be also present. The deletion size ranges from ~7 to 20 Mb, with the proximal breakpoint within or telomeric to subband 11q23.3 and the deletion extending usually to the telomere. The deletion is de novo in 85% of reported cases, and in 15% of cases it results from an unbalanced segregation of a familial balanced translocation or from other chromosome rearrangements. In a minority of cases the breakpoint is at the FRA11B fragile site. Diagnosis is based on clinical findings (intellectual deficit, facial dysmorphic features and thrombocytopenia) and confirmed by cytogenetics analysis. Differential diagnoses include Turner and Noonan syndromes, and acquired thrombocytopenia due to sepsis. Prenatal diagnosis of 11q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Management is multi-disciplinary and requires evaluation by general pediatrician, pediatric cardiologist, neurologist, ophthalmologist. Auditory tests, blood tests, endocrine and immunological assessment and follow-up should be offered to all patients. Cardiac malformations can be very severe and require heart surgery in the neonatal period. Newborns with Jacobsen syndrome may have difficulties in feeding and tube feeding may be necessary. Special attention should be devoted due to hematological problems. About 20% of children die during the first two years of life, most commonly related to complications from congenital heart disease, and less commonly from bleeding. For patients who survive the neonatal period and infancy, the life expectancy remains unknown

Health Care for Mitochondrial Disorders in Canada: A Survey of Physicians

BACKGROUND: An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care. METHODS: We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities. RESULTS: We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend "mitochondrial cocktails" for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority. CONCLUSIONS: While Canadian physicians' views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols

Rates of diagnostic transition and cognitive change at 18-month follow-up among 1,112 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL)

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not. Methods: Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. Results: The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. Conclusion: There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.12 page(s