Service d'Endocrinologie et Maladies Métaboliques, 1, Rue Polonovski, Hôpital C Huriez, Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille cedex, France.
Orphanet J Rare Dis. 2012 Jan 28;7:11. doi: 10.1186/1750-1172-7-11.
Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.
大多数先天性代谢缺陷（IEM）是隐性遗传的疾病，根据其机制可分为 3 大主要类型：细胞中毒、能量缺乏和复杂分子缺陷。它们可能与内分泌表现有关，这些表现可能是儿童期起病的先前诊断出的 IEM 的并发症。更罕见的是，内分泌疾病可能提示成人期的 IEM，当内分泌紊乱伴有多系统受累（神经、肌肉、肝脏特征等）时应怀疑存在 IEM。IEM 可影响所有腺体，但糖尿病、甲状腺功能障碍和性腺功能减退症是最常见的疾病。单一 IEM 可表现为多种内分泌功能障碍，尤其是涉及能量缺乏的疾病（呼吸链缺陷）以及金属（血色病）和贮积病（胱氨酸病）。非自身免疫性糖尿病、甲状腺功能障碍和/或甲状腺肿以及有时的甲状旁腺功能减退症应提示诊断为呼吸链缺陷。血色病常伴有性腺功能减退（常伴有糖尿病），而 Alström 病和胱氨酸病（均伴有糖尿病，后者也伴有甲状腺功能障碍）和半乳糖血症则表现为原发性性腺功能减退症。性腺功能减退症在 X 连锁肾上腺脑白质营养不良（伴肾上腺功能衰竭）、先天性糖基化紊乱、Fabry 病和糖原贮积病中也很常见（前 3 种疾病伴有甲状腺功能障碍，最后一种疾病伴有糖尿病）。这是一个新的、不断发展的领域，尽管其对生长、骨代谢和生育能力有影响，但在成年期尚未得到很好的认识。出于这个原因，管理成年患者的医生应该了解这些诊断。
