Primary Mitochondrial Disorders of the Pediatric Central Nervous System: Neuroimaging Findings.

Primary mitochondrial disorders (PMDs) constitute the most common cause of inborn errors of metabolism in children, and they frequently affect the central nervous system. Neuroimaging findings of PMDs are variable, ranging from unremarkable and nonspecific to florid and highly suggestive. An overview of PMDs, including a synopsis of the basic genetic concepts, main clinical symptoms, and neuropathologic features, is presented. In addition, eight of the most common PMDs that have a characteristic imaging phenotype in children are reviewed in detail. Online supplemental material is available for this article. ©RSNA, 2020.

The effects of nuclear DNA mutations on mitochondrial function.

ABSTRACT: The multiple functions of mitochondria, including adenosine triphosphate synthesis, are controlled by the coordination of both the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA) genomes. Mitochondrial disorders manifest because of impairment of energy metabolism. This article focuses on mutations in two nuclear genes and their effect on mitochondrial function. Mutations in the polymerase gamma, or POLG, gene are associated with multisystemic disease processes, including Alpers Syndrome, a severe childhood-onset syndrome. Mutations in the OPA1 gene are associated with autosomal dominant optic atrophy and other neurologic, musculoskeletal, and ophthalmologic symptoms. When assessing for disorders affecting energy metabolism, sequencing of both the mtDNA genome and the nDNA whole exome sequencing is necessary.

Genomics of aging: Reactive oxidation and inefficient mitochondria.

ABSTRACT: Many things are associated with decreased health and lifespan, including cancer, diabetes, atherosclerosis, high blood pressure, and chronic inflammatory conditions. Clinicians may not be familiar with the role that mitochondrial mutations and associated mitochondrial dysfunction play in a shortened lifespan. This article, the fifth in the JAANP Genomics of Aging series, describes the role that mitochondrial dysfunction plays in the development of age-related diseases such as Alzheimer disease, Parkinson disease, cancer, heart disease, and stroke.

Understanding the nomenclature of mitochondrial DNA mutations through examples of two specific disease entities: Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes and Leber hereditary optic neuropathy.

ABSTRACT: Mitochondrial diseases are genetic disorders that can arise either from maternally inherited mitochondrial DNA (mtDNA) or from mutations in nuclear DNA. This article is the second in a series of papers reviewing mitochondrial genetics and several of the disorders associated with mitochondrial gene variants. With a prevalence of 1:∼4,300 persons, mitochondrial disorders are diagnostic entities with which nurse practitioners should be familiar. In describing genetic mutations, numbering nucleotides (nuclear or mtDNA) is critical for communicating exactly where a variation has occurred in a stretch of nucleotides. This article discusses the nomenclature associated with mtDNA mutations, using the examples of mutations causing mitochondrial encephalopathy with lactic acidosis and stroke-like episodes and Leber hereditary optic neuropathy. Pathophysiology, symptoms, and treatment options for these disease entities are discussed.

Mitochondrial disorders: Understanding mitochondrial DNA point mutations and deletion syndromes.

ABSTRACT: Mitochondrial disorders arise from DNA mutations in either the mitochondrial DNA (mtDNA) or nuclear DNA genomes. This article focuses on a mtDNA base-pair mutation associated with neuropathy, ataxia, and retinitis pigmentosa and Leigh syndrome and the large-scale mtDNA deletion associated with Kearns-Sayre syndrome. Disease sequelae and management strategies are reviewed, along with implications for the nurse practitioner in primary or specialty care.

Mitochondrial DNA: Unraveling the "other" genome.

ABSTRACT: The mitochondrial genome, which contains all of the hereditary information within human mitochondria, consists of 16,569 base pairs of double-stranded DNA that encode 37 genes. Pathogenic mutations of mitochondrial DNA (mtDNA) cause dysfunction of the respiratory chain and the process of oxidative phosphorylation (OXPHOS), leading to impaired adenosine triphosphate synthesis. Nuclear DNA (nDNA) mutations can affect structural subunits or assembly factors of one of the five OXPHOS complexes. Mitochondrial diseases are a heterogeneous group of disorders, ranging from mtDNA single-point mutations and large-scale deletions to mitochondrial depletion syndromes, resulting from nDNA pathogenic mutations. Manifestations of mitochondrial disease are multisystemic, and organs with substantial energy requirements are most typically affected. Mitochondrial disorders are progressive in nature, and prognosis is dependent on the organs involved and the rate and severity of disease progression. A multidisciplinary team approach is needed to monitor and manage disease sequelae.

A Primer on Understanding Pediatric Health Care Quality Measurement.

Advanced practice registered nurses implement evidence-based care guidelines and assess the quality of care delivered to pediatric and adolescent populations to ensure that the highest standards of care are provided to the patients and their families. Standardized health care quality measures allow for assessment of clinical competence, monitoring of equitable health care distribution, improvement of provider/institutional accountability, development of standards for accreditation and certification, informing of quality improvement efforts, and creation of criteria for provider incentive payments. The purpose of this article is to explain why health care quality measures are established, what agencies oversee the development of meaningful pediatric quality measures, and how these measures inform and improve the care provided by pediatric-focused advanced practice registered nurses.

Collaboration Between PNPs and School Nurses: Meeting the Complex Medical and Academic Needs of the Child With ADHD.

Pediatric nurse practitioners take a lead role in diagnosing and coordinating the care of children with attention deficit hyperactivity disorder (ADHD). School nurses offer rich insight into the child's health and social and academic functioning in the school setting. School nurses develop individualized health care plans, administer and monitor medications, provide valuable input on Individualized Education Plans and Section 504 Accommodation Plans, and serve as the point person in communicating with the medical provider. Pediatric nurse practitioners can enhance the collaboration with school nurses by establishing communication parameters, streamlining medication regimens, and facilitating development of educational curricula for school nurses regarding evidence-based ADHD management. Optimizing partnerships with school nurses will provide better surveillance of treatment efficacy and can facilitate improved health and academic and social outcomes for children with ADHD.