These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

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FSGS is a renal manifestation of MCs. The renal lesion can precede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dysfunction caused by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or deafness.

Aims/hypothesis We assessed the prevalence and determinants of retinal and renal complications in patients with maternally inherited diabetes and deafness (MIDD).Methods This was a multicentre prospective study comparing the prevalence of retinopathy and renal disease in 74 patients with MIDD and 134 control patients matched for sex, age and clinical presentation at onset of diabetes, duration of diabetes and current treatment. Comparisons were adjusted for HbA 1c and hypertension. Diabetologia (2008) Results In MIDD patients, HbA 1c (7.6±1.6 vs 8.5±2.0%, p< 0.002), systolic blood pressure (126.6±16.2 vs 133.1± 17.3 mmHg, p<0.007) and prevalence of hypertension (33.8 vs 64.2%, p<0.0001) were lower than in control patients. Prevalence of diabetic retinopathy was 3.7-fold lower in MIDD patients (6/74, 8 vs 40/134, 29.6%, p< 0.0001). Differences between groups remained significant after adjustment for hypertension, systolic blood pressure and HbA 1c . In MIDD, urinary albumin excretion (314.8 vs 80.1 mg/24 h, p=0.035) and creatinine plasma levels (103.5 vs 82.2 µmol/l, p=0.0178) were higher and GFR was lower. Impaired renal function (GFR <60 ml/min) was four-to sixfold more frequent in MIDD. Differences between MIDD and control diabetic patients further increased when adjusted for HbA 1c and systolic blood pressure (p<0.0001). Adjustment for treatment with an ACE inhibitor or angiotensin II receptor antagonist did not modify the results. Conclusions/interpretation This study indicates that diabetic retinopathy is less prevalent in MIDD than in control diabetes. This suggests that retinal alterations due to mitochondrial disease may have a protective role. By contrast, nephropathy is far more frequent in MIDD, suggesting the presence of a specific renal disease independent of diabetic nephropathy.

BackgroundBoys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC) and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH) and primary defects in spermatogenesis.MethodsWe analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function.ResultsThe first symptoms appeared in the neonatal period (n = 5) or between 6 months and 8.7 years (n = 3). Basal plasma adrenocorticotrophic hormone (ACTH) concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH) test (n = 2), and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein.ConclusionsThe decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility.