Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases associated with a deficiency in the peroxisomal degradation of saturated very long chain fatty acids (VLCFA) resulting...Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases associated with a deficiency in the peroxisomal degradation of saturated very long chain fatty acids (VLCFA) resulting in an accumulation of VLCFA in the central and peripheral myelin, the adrenal cortex and the testis. Adrenal insufficiency with clinical hypocortisolism occurs in approximately two thirds of the patients with AMN. We studied the circulating adrenal hormones17α -hydroxyprogesterone (17α -OHP), androstenedione and dehydroepiandrosterone sulphate (DHEAS) in 63 male AMN patients (age 17- 65 years) and the DHEAS serum levels in 95 healthy male controls (age 30- 65 years). 34 of the patients presented with the phenotype of only spinal cord and peripheral nerve disability without hypocortisolism, 29 of the patients presented with the phenotype of either additional hypocortisolism or Addison’s syndrome only. Normal 17α - OHP concentrations were found in all patients with no significant difference between patients without and with hypocortisolism (6.07 ± 0.61 nmol/l and 4.76 ± 0.37 nmol/l). Androstenedione concentration was significantly (p < 0.01) lower in patients with hypocortisolism (2.99 ± 0.65 pmol/l versus 5.71 ± 0.68 pmol/l). As serum levels of DHEAS are age-dependent we divided the two groups into two subgroups each (subgroup one: age 17- 40 years, subgroup two: age 41- 65 years). The DHEAS concentration of patients without and with hypocortisolism was significantly (p < 0.01) lower in both subgroups (1: 4.35 ± 0.84 μ mol/l, n = 15, 2. 15 ± 0.28 μ mol/l, n = 19; 1: 1.90 ± 0.57 μ mol/, n = 21, 2: 0.96 ± 0.29 μ mol/l, n = 8) compared to controls (1: 9.0 ± 0.96 μ mol/l; 2: 5.21 ± 0.25 μ mol/l). In conclusion, androstenedione and DHEAS serum concentrations are subnormal in all AMN patients and may therefore serve as sensitive markers of the adrenal function in adrenomyeloneuropathy.展开更多
文摘性发育障碍(disorders sexdevelopment,DSD)是一类染色体性别、性腺性别、外生殖器性别不一致和性发育异常的先天性疾病。正常的性发育过程需要一系列基因、相关酶、因子的相互作用[1]。17β-羟类固醇脱氢酶3型(17β-hydroxysteroid dehydrogenase type 3,17β-HSD3)缺陷症是罕见的常染色体隐性遗传病,因17β-HSD3生成障碍或活性减低,致使睾酮合成障碍而致假两性畸形。本文就17β-HSD3缺陷症的临床特点及诊疗过程进行综述,旨在提高对该病的认识,及时对患者采取最佳治疗方案。
文摘Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases associated with a deficiency in the peroxisomal degradation of saturated very long chain fatty acids (VLCFA) resulting in an accumulation of VLCFA in the central and peripheral myelin, the adrenal cortex and the testis. Adrenal insufficiency with clinical hypocortisolism occurs in approximately two thirds of the patients with AMN. We studied the circulating adrenal hormones17α -hydroxyprogesterone (17α -OHP), androstenedione and dehydroepiandrosterone sulphate (DHEAS) in 63 male AMN patients (age 17- 65 years) and the DHEAS serum levels in 95 healthy male controls (age 30- 65 years). 34 of the patients presented with the phenotype of only spinal cord and peripheral nerve disability without hypocortisolism, 29 of the patients presented with the phenotype of either additional hypocortisolism or Addison’s syndrome only. Normal 17α - OHP concentrations were found in all patients with no significant difference between patients without and with hypocortisolism (6.07 ± 0.61 nmol/l and 4.76 ± 0.37 nmol/l). Androstenedione concentration was significantly (p < 0.01) lower in patients with hypocortisolism (2.99 ± 0.65 pmol/l versus 5.71 ± 0.68 pmol/l). As serum levels of DHEAS are age-dependent we divided the two groups into two subgroups each (subgroup one: age 17- 40 years, subgroup two: age 41- 65 years). The DHEAS concentration of patients without and with hypocortisolism was significantly (p < 0.01) lower in both subgroups (1: 4.35 ± 0.84 μ mol/l, n = 15, 2. 15 ± 0.28 μ mol/l, n = 19; 1: 1.90 ± 0.57 μ mol/, n = 21, 2: 0.96 ± 0.29 μ mol/l, n = 8) compared to controls (1: 9.0 ± 0.96 μ mol/l; 2: 5.21 ± 0.25 μ mol/l). In conclusion, androstenedione and DHEAS serum concentrations are subnormal in all AMN patients and may therefore serve as sensitive markers of the adrenal function in adrenomyeloneuropathy.
