Presentation and Diagnosis of Mitochondrial Disorders in Children

Abstract

The first disorder of mitochondrial function was described by Luft in 1959. Over the ensuing decades, multiple cases of mitochondrial dysfunction were reported, and the term "mitochondrial disorder" arose to describe any defect in the mitochondrial electron transport chain. The sequence of the mitochondrial genome was elucidated in 1981 by Anderson et al., and during the next 20 years, >200 pathogenic point mutations, deletions, insertions, and rearrangements were described. Most of the original cases were adults, and the diagnosis of a mitochondrial disorder in an adult patient became relatively straightforward. Adults present with well-defined "mitochondrial syndromes" and generally carry mitochondrial DNA mutations that are easily identified. Children with mitochondrial disorders are much harder to define. Children are more likely to have a nuclear DNA mutation, whereas the "classic" syndromic findings tend to be absent. This review describes both the varying presentations of mitochondrial disorders and the common laboratory, imaging, and pathologic findings related to children.

Multimodal Anesthesia for Glaucoma Surgery in a Child with Mitochondrial Disease and Malignant Hyperthermia

“…This case report highlights two important points; [1] the value of a multidisciplinary team to optimize preoperative status, and [2] the benefit of judicious selection of anesthetic technique in order to avoid complications, such as lactic acidosis, MH or PRIS. Finally, this case underscores the benefit of regional anesthesia in reducing anesthetic requirements and facilitating an uneventful transition from the operating room to post anesthesia care unit.…”

“…The disorder has an incidence of 1:5000 live births [1], and affects tissues with high-energy requirements such as the central nervous system, retina, heart and muscle [2]. Consequently, these patients have multiple comorbidities that include cardiac, endocrine, and neurologic dysfunction [3][4][5].…”

Sleep disordered breathing in children with mitochondrial disease

“…The symptoms are varied and many organ systems are involved [12]. Approximately 45% of pediatric patients with MD first present with a neuromuscular problem [13,14]; however, the character and degree of neuromuscular impairment are poorly defined.…”

“…SDB in children with primary MD has not been defined. Although the exact incidence of MD remains unknown, the prevalence of MD is higher than many of the more recognized inherited NMDs, such as Duchenne's muscular dystrophy [12]. Recommendations regarding polysomnography do not exist for patients with MD, even though they may have a high potential to develop SDB.…”

Decreased exhaled nitric oxide levels in patients with mitochondrial disorders

“…Adults typically present with welldefined "mitochondrial syndromes" resulting from mitochondrial DNA mutations that are easily identified. Children with MD are much harder to identify because children are more likely to have nuclear DNA mutations and the "classic" mitochondrial syndromic findings are typically absent [1]. Over the last few decades, diagnostic criteria have been developed to assist in the recognition and diagnosis of MD.…”