From: Endocrine manifestations related to inherited metabolic diseases in adults
DISEASES | CLINICAL MANIFESTATIONS | ENDOCRINE DYSFUNCTION: HYPOGONADISM | DIAGNOSIS | TREATMENT |
---|---|---|---|---|
Intoxication diseases | Â | Â | Â | Â |
Haemochromatosis | Melanodermy Hepatomegaly Rheumatologic signs Early heart involvement in juvenile forms Cirrhosis and hepatocarcinoma | Hypogonadotrophic hypogonadism - 5%-10% (HFE1)- early-onset in HFE-2 with hear involvementDiabetes 10% Hypo- and hyperthyroidism: ≤ 1% Adrenal insufficiency, hypopituitarism, and hypoparathyroidism: similar to the general population (except for secondary iron overload) | Transferrin saturation Serum ferritin Leukocytes HFE gene mutation | Phlebotomy Iron chelation Androgen with caution due to a possible increased risk of hepatocarcinoma |
Galactosaemia | Mental retardation Cataracts Osteoporosis | Hypergonadotropic hypogonadism: 75-96% | Blood and urine measurement of galactose and galactitol Leukocytes GALT gene mutation | Galactose-free diet Oestrogen from 12-13 years; then + progestins Discuss recombinant FSH/oocyte cryopreservation Osteoporosis: Calcium ± vitamin D ± diphophonates |
Complex molecules disorders | Â | Â | Â | Â |
X-linked adrenoleukodystrophy | Progressive central and peripheral nervous system demyelination in boys | Clinical hypogonadism: 2/3 Erectile dysfunction: 58% Small testes: 12% Primary adrenal failure involving both gluco and mineralosteroid: 70% in adults | Low testosterone12% Inadequate response to HCG: 88% High LH:16% and FSH levels: 32% High testosterone/DHT ratio High VLCFA Leukocytes ABCD 1 gene mutation | Lorenzo oil Blood marrow transplantation Gene therapy |
Perrault syndrome or D-bifunctional protein deficiency | Hearing loss Ataxia | Ovarian dysgenesis | Leukocyte HSD17β4 gene mutation, Sometimes mitochondrial DNA mutation |  |
Congenital disorders of glycosylation Most are protein hypoglycosylation diseases | Affect nearly all organs and systems Often a significant neurological component. | Hypogonadism with small testes or amenorrhea Hypo-, hypergonadotropic or mixed hypogonadism Sometimes hyperprolactinaemia Abnormal TSH Insulin resistance related to peculiar fat repartition | N-glycosylation diseases: serum transferrin isoelectrofocusing O-glycosylation disorders: apo CIII isoelectrofocusing Leukocytes gene mutation | Inhibitors of phosphomannose isomerase under evaluation in CDG-Ia Mannose in CDG-Ib |
Cystinosis | 3 forms: infantile, juvenile, ophthalmic (adulthood) Liver and muscle involvement Progression to end-stage renal disease | Hypergonadotropic hypogonadism 74% in males (gonadotropin levels above the normal range and testosterone levels in the low normal range); Delayed puberty Hypothyroidism > 50% Insulin-dependant diabetes Growth failure | Gluco-phospho-aminic diabetes Hypokalaemia, acidosis, Leukocyte cystin measurement CTNS gene mutation | Electrolyte supplementation Vitamins Indomethacin Cysteamine |
Fabry disease | Acroparaesthesias in boys Angiokeratoma Stroke at young age Renal, heart and eye involvement | Hypothyroidism Isolated case report of subclinical adrenal insufficiency and hypoparathyroidism Infertility, osteoporosis | Alpha-galactosidase A in males GLA gene mutation in females (X-linked) | Substitutive recombinant enzyme therapy |
Alström syndrome | Short height Renal failure Dilated myocardiopathy Blindness, Deafness | Early insulin resistant diabetes - Childhood obesity Primary hypogonadism (in males) PCOS and hirsutism in female Hypothyroidism | Major Hypertriglyceridaemia HypoHDLemia Leukocytes ALMS I gene mutation |  |
Selenoprotein deficiency disorder | Myopathy, Dermal photosensitivity | Oligospermia | low serum T3 and and high serum T4 Reduced selenoprotein concentrations Leukocytes SECISBP2 gene mutation | Selenium supplementation not efficient on hormone thyroid profile |
Energy defect | Â | Â | Â | Â |
Mitochondrial cytopathies | See Table 2 or 3 Maternal inheritance | Hypogonadotropic hypogonadism: 20% t- 30% delayed growth and puberty | See Table 2 or 3 | See Table 2 or 3 |
Glycogenosis | Liver involvement Infections in type Ib Renal complications in adulthood | Children: fasting ketosis hypoglycaemia; growth failure Adults: I, III types: polycystic ovary syndrome, diabetes, osteoporosis VI, IX types: spontaneous recovering delayed puberty autoimmune hypothyroidism in type I b | hyperlipaemia, hyperlactataemia, hyperuricaemia Leukocytes gene mutation | Frequent food intake, uncooked cornstarch Low carbohydrate glycaemic index Night enteral feeding G-CSF in Ib type, allopurinol Avoid oestroprogestative pills |