Table 3 Main inborn errors of metabolism associated with thyroid dysfunction
From: Endocrine manifestations related to inherited metabolic diseases in adults
DISEASES | CLINICAL MANIFESTATIONS | ENDOCRINE DYSFUNCTION: DYSTHYRODISM | DIAGNOSIS | TREATMENT |
|---|---|---|---|---|
Energy defect | Â | Â | Â | Â |
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 Adults: I, III types: polycystic ovary syndrome, diabetes, osteoporosis VI, IX types: spontaneous recovering delayed puberty | Fasting hypoglycaemia Hyper-lipaemia, -uricaemia Hyperlactataemia: - 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 | Â | Â | Â | Â |
Fabry disease | Acroparesthesia Angiokeratoma 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 (X-linked) | 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 Vitamins Indomethacin Cysteamine |
Type 1 hyperoxaluria | Recurrent oxalic lithiasis leading to end stage renal disease Bone, eye, heart involvement | Hypothyroidism - often severe - sometimes signalling disease | Hyperoxaluria Hyperglycoluria 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 Hepatomegaly 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 (X-linked) | 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 Hypogonadism | 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 Oligospermia | Leukocytes SECISBP2 gene mutation | Â |
Intoxication disorders | Â | Â | Â | Â |
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 | Phlebotomy Iron chelation |