Phenotype variability in 130 adult patients with respiratory chain disorders

Despite continuously improving diagnostic facilities, respiratory chain dis orders (RCDs) are easily overlooked or misdiagnosed. We thus Studied phenot ype variability and the diagnostic pootential or clinical and laboratory in vestigations in patients with RCD. We retrospectively evaluated clinical an d laboratory investigations in 130 patients with RCD: 63 women and 67 men, aged 17-87 years, diagnosed between January 1992 and December 1999. mtDNA m utations were found in 20 patients, a respiratory chain defect but no mutat ion in 4; an abnormal lactate stress test but no mutation or biochemical de fect in 66; and ragged-red fibres or reduced oxidative enzyme staining but no mutation, biochemical defect or abnormal lactate stress test in 40 patie nts. The most frequent initial manifestation of RCD were limb weakness, mus cle pain and sensory disturbances. The most frequent clinical findings at d iagnosis were muscle pain, fatiguability, limb weakness, reduced tendon ref lexes and Muscle wasting, irrespective of the diagnostic evidence. Mean age at onset, disease duration and time until diagnosis were 39, 14 and 13 yea rs, respectively, without sex differences. The family history was positive in 29% of the patients. Hyperlipidaemia was found in 45%, hyper-CK-aemia in 42%, short stature in 33%, thyroid dysfunction in 17%, diabetes in 12%, an d epilepsy in 8% or the patients. Laboratory investigations that prove usef ul to support the diagnosis of RCD are muscle biopsy, electromyography, lac tate stress testing, echocardiography and mtDNA analysis. Systems most ofte n involved in RCDs were the PNS, CNS, endocrine system and heart. The diagn osis of RCD requires awareness of the great phenotypic heterogeneity and an individualized, integral, multidisciplinary approach.