Abstract
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.
Highlights
Inborn errors of metabolism (IEM) are rare genetic diseases, which usually have a recessive mode of inheritance
The aim of this review is to identify the main IEMs in adults that can be revealed or complicated by an endocrine disorder other than hypoglycaemia
With the exception of iron overload, IEM are very rare disorders. They may be associated with endocrine disorders, most of which are linked to carbohydrate metabolism disturbances, thyroid dysfunction and hypogonadism
Summary
Inborn errors of metabolism (IEM) are rare genetic diseases, which usually have a recessive mode of inheritance. Diabetes may complicate a previously diagnosed IEM, those inducing impairment of the degradation or synthesis of complex molecules In this group, hypothyroidism or hypogonadism are frequently associated endocrine disorders. Diabetes, mainly linked to ß cell dysfunction, is encountered in the 3 types of IEM: intoxication disorders (mainly haemochromatosis, sometimes organic aciduria), disorders of energy metabolism (respiratory chain defects, GSD) or organelle disorders (Alström and Rogers syndromes, cystinosis) Of these IEM, iron overload has a special place in adulthood since hereditary haemochromatosis linked to a mutation of the HFE 1 gene is one of the most frequent metabolic diseases, even if its penetrance is variable and is modulated by environmental factors such as body weight and alcohol. Further investigations, including GH (Growth Hormone) dynamics, are needed to determine whether disturbances in the GH/IGF axis contribute to this relatively short stature, the origin of which is probably multifactorial through decreased renal function, feeding difficulties, hypothyroidism, hypogonadism, etc
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