Table 1.

Endocrine manifestations of inborn errors of metabolism in adults

IEM General classification	IEM associated with endocrine manifestations and most important mechanism	ENDOCRINE MANIFESTATIONS
		Diabetes	Dysthyroidism	Hypopara- thyroidism	Adrenal failure	Hypogonadism	Hypopituitarism
INTOXICATION Metal intoxication Haemochromatosis Aceruleoplasminemia Wilson's Sugar intolerances Galactosaemia Most organic acidurias	Haemochromatosis Iron storage	Diabetes 10%	< 1%	< 1%	< 1%	Hypogonadotropic 5-10%	< 1% except for acquired iron overload and hypogonadism
	Aceruloplasminemia Iron storage	Diabetes					rare
	Wilson's disease Copper storage			Hypoparathyroidism rare
	Galactosaemia Galactose metabolites					Hypergonadotropic in female	Short stature
	Organic aciduria Organic acids	Possible ketoacidosis pancreatitis
ENERGY DEFECT Mitochondrial disorders: Respiratory chain disorders Fatty acid oxidation defects	Respiratory chain defect Deficient energy production	Diabetes	All types of thyroid dysfunction	Hypoparathyroidism rare	Subclinical adrenal failure	Hypogonadotropic	Hypopituitarism Short stature 30 to 50%
	LCHAD Deficient energy production			Hypo- parathyroidism
Cytoplasmic energy defects Disorders of glycogen metabolism	Glycogenosis Glycogen storage (type I, III)	Diabetes	Thyroid dysfunction (type Ib)			Mixed or undetemined PCOS (type I)
COMPLEX MOLECULES Peroxisomal disorders	X-linked adreno-leukodystrophy Perrault syndrome VLCFA accumulation				Adrenal failure	Mixed or undetemined (mainly hypergonadotropic)
Lysosomal disorders	Fabry disease Globoside storage in lysosomes		Subclinical hypothyroidism		Subclinical adrenal failure	Infertility
	Cystinosis Cystine in lysosomes	Diabetes	Hypothyroidism 75%			Hypergonadotropic	Short stature 30 to 50%
Disorders of intracellular trafficking and processing such as Congenital disorders of glycosylation Inborn errors of cholesterol synthesis.	CDG I Abnormal glycosylated proteins		Congenital hypothyroidism			Mixed or undetermined mainly hypergonadotropic
	Multisystemic triglyceride storage disease Triglyceride storage in endoplasmic reticulum		Thyroid dystrophy
	Type 1 hyperoxaluria Oxalate		Hypothyroidism				Advanced bone age
	Type B Niemann-Pick disease Sphingolipid storage in lysosomes				Partial rare		Short stature
TRANSPORTER DEFECT	Rogers syndrome: Thiamine-sensitive megaloblastic anaemia Defective ATP production in ß cells	Diabetes
	MCT8 deficiency Defective T3 transport in neurons		High blood T3
	Alström syndrome	Diabetes	Hypothyroidism			Hyper- and hypogonadotropic (men) PCOS in women	Rare hypopituitarism Initial advanced bone age
	Selenoprotein deficiency disorder		Low T3-High T4			Oligospermia	Short stature

CDG: congenital disorders of glycosylation; IEM: inborn errors of metabolism; LCHAD: long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; MCT8: Monocarboxylate transporter; PCOS: polycystic ovary syndrome; T3: triiodothyronine; T4: thyroxine; VLCFA: Very long chain fatty acids.