Endocrine manifestations related to inherited metabolic diseases in adults

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.

Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases

“…These may include liver failure, renal failure, malnutrition, psychosocial causes or primary disease (2). There are a small number of hypopituitarism-induced growth retardation cases reported in the relevant literature, such as a few mitochondrial cytopathies (5) and iron-overload diseases (6,7,8).…”

“…There are a small number of hypopituitarism-induced growth retardation cases reported in the relevant literature, such as a few mitochondrial cytopathies (5) and iron-overload diseases (6,7,8). Growth retardation may occur in approximately 30%-60% of patients with mitochondrial cytopathy, cystinosis, and galactosemia (2). In our study, the overall proportion of growth retardation was 10.5%; however, this figure was 25% in patients with mitochondrial disease, and no growth retardation was observed in our seven patients with galactosemia (Table 1).…”

“…Many endocrine glands are affected; however, diabetes mellitus (DM), thyroid dysfunction, and gonadal deficiency are more frequent (2). Endocrine disorders, especially DM, also tend to be more common in patients with mitochondrial diseases (3).…”

“…It is notable that many latent endocrine dysfunctions may be concomitant with Fabry disease and could be life threatening (4). As IMDs may be accompanied by serious endocrine dysfunctions, being aware of the condition and early diagnosis by simple tests are crucial to preventing possible complications (2). …”

Current situation and prospects of newborn screening and treatment for Phenylketonuria in China - compared with the current situation in the United States, UK and Japan

“…Phenylketonuria (PKU) is an inborn error of metabolism, usually caused by a deficiency of phenylalanine hydroxylase which can lead to mental retardation and neurobehavioral abnormalities (1). The overall incidence of PKU in the world varies widely in different human populations such as 1 in 15,000 births in the United States (2,3), 1 in 10,000 births in United Kingdom (4,5), 1 in 2,600 births in Turkey (6) and fewer than 1 in 100,000 births in Japan (7,8).…”