Clinical Heterogeneity in Mitochondrial DNA Deletion Disorders: A Diagnostic Challenge of Pearson Syndrome

Abstract

The clinical presentation of mitochondrial DNA (mtDNA) disorders is quite diverse. Very often, the initial symptoms do not fit a specific disease, and diagnosis is difficult to make. We describe a patient who presented with macrocytic anemia. Extensive biochemical and clinical work-up failed to provide an etiology for the macrocytic anemia. The patient over the course of 6 years developed gait problems, exercise intolerance, episodic vomiting, short stature, dermatological problems, and recurrent infection. At age 8 years she had encephalopathy with ataxia and dysphagia. The presence of elevated lactate, bilateral basal ganglia calcification, and ragged red fibers led to mtDNA mutational analysis. A novel 4.4-kb deletion from nucleotide position 10,560 to nucleotide position 14, 980 was identified in muscle biopsy. The same heteroplasmic mtDNA deletion was present in blood, buccal cells, and hair follicles, but not in mother's blood, consistent with sporadic mutation in the patient. This case emphasizes the importance of considering mtDNA disorder in patients with multisystemic symptoms that cannot be explained by a specific diagnosis.

Legionella pneumophilamultiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells

“…Other reports have indicated that children and adults with mitochondrial disorders have a high risk of recurrent infection (Edmonds et al, 2002;Edmonds, 2004;Wortmann et al, 2006). Furthermore, recurrent infection has been reported in individuals with specific mitochondrial diseases such as Kearns-Sayre syndrome (Katsanos et al, 2002) and Pearson syndrome (Lacbawan et al, 2000).…”

“…Depending on which tissues are affected most severely, the phenotypic outcomes are diverse and can include diabetes, blindness, deafness, stroke-like episodes, epilepsy, ataxia, muscle weakness, exercise intolerance and kidney disease (Wallace et al, 1988;Goto et al, 1992;Tatuch and Robinson, 1993;Mackey et al, 1996;Geromel et al, 2001;Rossignol et al, 2003;McKenzie et al, 2004). A number of reports suggest that mitochondrial disease patients are more susceptible to recurrent bacterial infections, particularly of the respiratory tract (Lacbawan et al, 2000;Edmonds et al, 2002;Katsanos et al, 2002;Ogawa et al, 2003;Edmonds, 2004;Wortmann et al, 2006). However, the mechanisms that underlie such increased susceptibility have not been studied and are not understood.…”

Multiorgan disorder syndrome (MODS) in an octagenarian suggests mitochondrial disorder

“…Dermatological abnormalities in MIDs are rare but have been occasionally reported 3 . Dermatological abnormalities associated with MIDs include psoriasis, skleroderma, neurodermitis, atopic dermatitis, hyperpigmentation, flaky skin 3 , transient alopecia 3 , asymmetric vascular dilatation, purpuric macules of the sole and palma, lentiges, cutaneous zygomycosis 4 , dermal lipomata, or local melanoderma (Table 2). Dermatological abnormalities in MIDs often go undetected and are frequently not regarded as a manifestation of a MID.…”

Pearson Sendromlu Bir Olguda Mitokondrial Miyopati Rehabilitasyonu

“…Tüm hastaların kemik iliğinde myeloid ve eritroid prekürsörleri vakuolizedir, birçoğunda eritroblast azalmıştır ve hepsi sideroblast ve çoğu ring sideroblasttır. Altı yaşa gelen hastalarda yürüme problemleri, egzersiz intoleransı, kısa boy, dermatolojik problemler ve rekürren enfeksiyonlar gelişir (1,(6)(7)(8). Bizim hastamızda da anemi, laktik asidoz ve kemik iliği aspiratında miyeloid ve eritroid seride vakuolizasyon ve megaloblastik değişiklikler, yürüme problemi, egzersiz intoleransı ve büyüme geriliği mevcuttu.…”