10 research outputs found
CASE REPORT <br>Leigh disease: 9 years follow up of a Polish family harboring T8993C mitochondrial DNA mutation
Leigh disease (LD) or subacute necrotizing encephalomyelopathy (SNE) is a mitochondrial dysfunction. It can be caused by either mitochondrial or nuclear DNA mutations, which impair communication of the complexes of the human electron transporting chain (ETC) directly or by interfering with nucleus-mitochondrion. Leigh disease is characterized by psychomotor retardation, muscle weakness, pyramidal signs, lactic acidosis, hypotonia, dysphagia, symmetric basal ganglia and brainstem lesions. Due to a relatively small number of published cases and multisystemic involvement of LD there is no clear definition of symptoms and definite diagnosis can be based only on the genetic analyses. In our study we describe a Polish family harboring T8993C mutation in one of the subunits of ETC complex V (ATPase). We present the differential diagnosis of LD and observations of the described family performed 9 years from the diagnosis of Leigh disease. We suggest that the results of the neurophysiologic examinations in LD patients are characteristic both for neuronal and muscular lesions. Apart from that we assessed physical or psychological state of the family members measured by self-constructed LD-specific quality of life questionnaire
Postlingual hearing loss as a mitochondrial 3243A>G mutation phenotype.
BACKGROUND: The prevalence of isolated hearing loss (HL) associated with the m.3243A>G mutation is unknown. The aim of this study was to assess the frequency and heteroplasmy level of the m.3243A>G mutation in a large group of Polish patients with postlingual bilateral sensorineural HL of unidentified cause. METHODOLOGY/PRINCIPAL FINDINGS: A molecular search was undertaken in the archival blood DNA of 1482 unrelated patients with isolated HL that had begun at ages between 5 and 40 years. Maternal relatives of the probands were subsequently investigated and all carriers underwent audiological tests. The m.3243A>G mutation was found in 16 of 1482 probands (an incidence of 1.08%) and 18 family members. Of these 34 individuals, hearing impairment was detected in 29 patients and the mean onset of HL was at 26 years. Some 42% of the identified m.3243A>G carriers did not develop multisystem symptomatology over the following 10 years. Mean heteroplasmy level of m.3243A>G was lowest in blood at a level of 14% and highest in urine at 58%. These values were independent of the manifested clinical severity of the disease. CONCLUSIONS: A single m.3243A>G carrier can usually be found among each 100 individuals who have postlingual hearing loss of unknown cause. Urine samples are best for detecting the m.3243A>G mutation and diagnosing mitochondrially inherited hearing loss
Comparison of clinical status among all groups of patients (I, II and III) carrying m.3423A>G mutation: I = Multi-symptomatic subgroup, II = Isolated HL subgroup, III = Asymptomatic subgroup.
*<p>2 patients had only part 2 assessed.</p>**<p>11/12 patients were assessed.</p>***<p>probably false positive related to high score for quality of life (part 1) of two patients.</p><p>HL = hearing loss; NMDAS = Newcastle Mitochondrial Disease Adult Scale; MRS = magnetic resonance spectroscopy,</p><p>LA = lactic acidosis, MGCA = 3-methylglutaconic aciduria, MRI = magnetic resonance imaging; NA = not applicable.</p><p>GC-MS = Gas Chromatography–Mass Spectroscopy.</p><p>Degree of HL: mild HL<40 dB; moderate 41–70 dB; severe 71–90 dB; profound >91 dB.</p
Heteroplasmy level of the m.3243A>G mutation in examined tissues.
<p>Above: the scores of patients with multi-symptomatic presentation (subgroup I). Below: the scores of patients with isolated hearing loss and asymptomatic carriers (subgroups II and III together).</p
The sequences of the primers M_F and M_R.
<p>The sequences of the primers M_F and M_R.</p
Heteroplasmy levels (% of total tissue DNA) of m.3243A>G mutation in mtDNA samples isolated from: urinary sediment, hair follicles, buccal mucosa, nails and blood (put in order of heteroplasmy intensity).
<p>F = female, M = male, yrs = years, NA = not applicable.</p><p>The subgroups of patients: I – multi-organ presentation, II - isolated hearing loss and III - asymptomatic are presented separately.</p
Latest audiograms of the three patients shown in <b>Figs. 1</b> and <b>2</b>.
<p>Patients 15 and 29 have become cochlear implant users. The HL threshold of patient 28 has still not changed.</p
Characteristics of the patients carrying the m.3243A>G mutation patients 1–17 with multi-organ presentation (subgroup I), patients 18–29 with isolated hearing loss (subgroup II), and asymptomatic carriers 30–34 (subgroup III).
<p>Probands are shown in bold.</p><p>GC-MS = gas chromatography–mass spectroscopy; NMDAS = Newcastle Mitochondrial Disease Adult Scale; MGCA = 3-methylglutaconic aciduria; LA = lactic aciduria; HL = hearing loss; NP = not performed; NA = normal value; QoL = quality of life; CI = cochlear implant user; IMGP = increased mineralisation of globus pallidus; MCA = minimal cerebellar atrophy; MRS = magnetic resonance spectroscopy; MRS score: 0 = negative LA, 1 = uncertain LA, 2 = positive LA, 3 = strong LA.</p><p>C = cardiomyopathy; DM = diabetes mellitus; H = migraine; I = infertility; K = renal insufficiency; M = myopathy; N = peripheral neuropathy; RP = pigmentary degeneration of retina; S = stroke-like episodes; SS = short stature.</p><p>No HL = normal hearing.</p>*<p>Stress = hearing deterioration following stressful event; Aminogly = hearing deterioration following aminoglycoside administration; Noise = hearing deterioration following noise exposure; Pancreatitis = hearing deterioration following acute pancreatitis; Pregnancy = hearing deterioration after pregnancy.</p