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Table 3 Main inborn errors of metabolism associated with thyroid dysfunction

From: Endocrine manifestations related to inherited metabolic diseases in adults

Energy defect     
Mitochondrial disease Involving seemingly unrelated organs
Maternal inheritance
Deafness, retinitis pigmentosa
Short stature,
Neuromuscular symptoms
Kidney insufficiency
Goiter, hypo-/hyperthyroidism, thyrotropic insufficiency
Non-autoimmune diabetes in a lean patient > 30 years
More rarely hypoparathyroidism, adrenal insufficiency, hypogonadism, hypopituitarism
Blood lactate/pyruvate ratio (high)
Blood ßOH butyrate/acetoacetate ratio: high
CSF lactate (high)
Urinary organic acids
Plasma amino acids: high alanine & proline
Muscle biopsy
Mitochondrial DNA study
Discuss coenzyme Q10
Glycogenosis Liver involvement
Infections in type Ib
Growth failure
Renal complications in adulthood
Increased prevalence of autoimmune hypothyroidism in type I b
Children: fasting ketotic hypoglycaemia
I, III types: polycystic ovary syndrome, diabetes, osteoporosis
VI, IX types: spontaneous recovering delayed puberty
Fasting hypoglycaemia
Hyper-lipaemia, -uricaemia
- fasting predominant: type I
- postprandial predominant: type III, VI, IX
Leukocytes DNA gene mutation
Frequent food intake
Uncooked cornstarch
Low carbohydrate glycaemic index
Night enteral feeding
G-CSF in Ib type, Allopurinol
Avoid oestroprogestative pills
Degradation and synthesis of complex molecules     
Fabry disease Acroparesthesia
Stroke at young age
Renal, heart and eye involvement in boys
Subclinical hypothyroidism
Isolated case report of subclinical adrenal insufficiency and hypoparathyroidism
Infertility, osteoporosis
Alpha-galactosidase A in males
Leukocytes GLA gene mutation in females
Substitutive recombinant
enzyme therapy
Cystinosis 3 forms: infantile, juvenile, ophthalmic (adulthood)
Liver and muscle involvement
Evolution to end stage renal disease
Hypothyroidism > 50%
Hypergonadotropic hypogonadism (in males)
Insulin-dependant diabetes
Growth failure
Gluco-phospho-aminic diabetes
Hypokalaemia, acidosis,
Leukocyte cystin measurement
Leukocytes CTNS gene mutation
Electrolyte supplementation
Type 1 hyperoxaluria Recurrent oxalic lithiasis leading to end stage renal disease
Bone, eye, heart involvement
- often severe
- sometimes signalling disease
Alanine-glyoxylate-aminotransferase measurement on liver biopsy
Leukocytes AGXT gene mutation
Abundant hydration
Urine alkalinisation
Pyridoxine phosphate
Kidney and liver transplantation
Neutral lipid storage disease Ichtiosis or Chanarin-Dorfman syndrome
or myopathy/cardiomyopathy
Central nervous system involvement
Nodular dystrophy of the thyroid
(clear cells follicular adenoma)
Normal lipid levels
CPK sometimes moderately increased
Accumulation of triglycerides
- in leukocytes (Jordan's abnormality)
- in muscle, skin fibroblasts, liver (steatosis)
Leukocytes or fibroblasts ABHD5 or PNPLA2 gene mutation
No effective treatment
MCT8 deficiency
Or Allan-Erndon-Dudley syndrome
Severe cognitive deficiency,
Hypotonia and dystonic movement
Progressive spastic quadriplegia in boys
High serum T 3 - low serum rT3
Low serum T4 (sometimes normal)
Normal serum TSH (or slightly elevated)
Nodular dystrophy of the thyroid
Leukocytes MCT8 gene mutation
Propylthiouracil and L- thyroxin
Congenital disorders of glycosylation Affect nearly all organs and systems
Often, significant neurological component.
Most of the time difficulties in TSH measurement
Always check with a reference method
Rare congenital hypothyroidism
N-glycosylation diseases:
serum transferrin isoelectrofocusing
O-glycosylation disorders:
apo CIII isoelectro-focusing,
leukocytes DNA molecular study
Inhibitors of phosphomannose isomerase under evaluation in CDG-Ia
Mannose in CDG-Ib
Selenoprotein deficiency disorder Myopathy,
Dermal photosensitivity
Deficiency of deiodinases: low serum T3 and and high serum T4
Leukocytes SECISBP2 gene mutation  
Intoxication disorders     
Haemochromatosis Liver, rheumatologic and heart involvement Hypo- and hyperthyroidism: ≤ 1%
Diabetes (10%)Peripheral hypogonadism (5-10%)
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
  1. Abbreviations 3,3',5-triiodothyronine: T3; 3,3',5'-triiodothyronine: reverse T3 or rT3; tetraiodothyronine: thyroxine or T4; ATGL or Adipose triglyceride lipase, encoded by the gene PNPLA2 or patatin-like phospholipase domain containing 2; or alpha/beta-hydrolase domain-containing protein 5, encoded by ABHD5 gene (also called comparative gene identification-58); AGTX or Alanine-glyoxylate-aminotransferase gene; CDG or congenital disorders of glycosylation; CPK: creatin phospho kinase; CSF: cerebrospinal fluid; MCT8 (Monocarboxylate Transporter 8) deficiency or Allan-Erndon-Dudley syndrome or SLC16A2-Specific Thyroid Hormone Cell Transporter Deficiency; SECISBP2 or Sec insertion sequence-binding protein 2 (also known as SBP2)