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Table 4 Main IEM associated with hypogonadism

From: Endocrine manifestations related to inherited metabolic diseases in adults

Intoxication diseases     
Haemochromatosis Melanodermy
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
Iron chelation
Androgen with caution due to a possible increased risk of hepatocarcinoma
Galactosaemia Mental retardation
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     
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
Leukocytes ABCD 1 gene mutation
Lorenzo oil
Blood marrow transplantation
Gene therapy
Perrault syndrome or D-bifunctional protein deficiency Hearing loss
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
Fabry disease Acroparaesthesias in boys
Stroke at young age
Renal, heart and eye involvement
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
Major Hypertriglyceridaemia
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     
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
  1. All autosomal recessive unless otherwise indicated
  2. Abbreviations: DHT: Dihydrotestosterone; G-CSF: Granulocyte colony-stimulating factor; GALT: galactose-1-phosphate uridyltransferase; HSD17B4: 17beta-hydroxysteroid dehydrogenase type 4 (also known as D-bifunctional protein (DBP). PCOS: Polycystic ovary syndrome; VLCFA: Very long chain fatty acids.