Clinical heterogeneity in mitochondrial DNA deletion disorders: A diagnostic challenge of Pearson syndrome

The clinical presentation of mitochondrial DNA (mtDNA) disorders is quite d iverse. Very often, the initial symptoms do not fit a specific disease, and diagnosis is difficult to make, We describe a patient who presented with m acrocytic anemia. Extensive biochemical and clinical work-up failed to prov ide an etiology for the macrocytic anemia. The patient over the course of 6 years developed gait problems, exercise intolerance, episodic vomiting, sh ort stature, dermatological problems, and recurrent infection. At age 8 yea rs she had encephalopathy with ataxia and dysphagia, The presence of elevat ed lactate, bilateral basal ganglia calcification, and ragged red fibers le d to mtDNA mutational analysis, A novel 4.4-kb deletion from nucleotide pos ition 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 mut ation in the patient. This case emphasizes the importance of considering mt DNA disorder in patients with multisystemic symptoms that cannot be explain ed by a specific diagnosis. Am. J, Med. Genet. 95:266-268, 2000. 2000 Wiley -Liss, Inc.