Metals are indispensable elements of cell biology. They function
as cofactors in many specific proteins and are involved in all major metabolic
pathways. Their metabolism and implications in inborn errors of
metabolism are still not well known, but the number of inherited
metabolic disorders involving the absorption, transport, or metabolism
of metals is rapidly growing. Clinical presentations are very diverse
and can involve all organs and systems, including the liver and
the central nervous system (Table 169-1).
Deficiency in metals results in metabolic abnormalities due mostly
to loss of function of metal-dependent proteins. On the other hand,
excess of metals can result in the unregulated oxidation of proteins,
lipids, and other cellular components, causing subsequent tissue
injury. Some inherited metal disorders are treatable by chelating drugs
or by daily supplementation of the missing metal at pharmacological
Table 169-1. Inborn
Errors of Metal Transport and Metabolism |Favorite Table|Download (.pdf)
Table 169-1. Inborn
Errors of Metal Transport and Metabolism
|Metal||Disease||Genetics||Defect||Clinical Presentation||Diagnostic Tests||Treatment|
|Copper||Wilson disease||ATP7b loss of function (AR)||Biliary copper excretion resulting in copper
accumulation||Childhood: liver||↓ Ceruloplasmin
and total Cu in serum||Cu chelators:|
|↑ Free Cu in serum||Trientine|
|↑ Cu in liver and urine|
|DNA testing||Ammonium tetrathiomolybdate|
|Menkes syndrome||ATP7a loss of function (X-linked)||Cu transport across the placenta, brain and
gastrointestinal (GI) tract||Menkes: Early infancy: neurological, collagen||↓ Ceruloplasmin
and Cu in serum abnormal plasma/CSF catecholamine ratio||Subcutaneous copper histidine (< 10 days of
|Occipital horn syndrome|
|Occipital horn syndrome: mild variant, no neurological involvement||DNA testing|
|Iron||Hemochromatosis (adult)||HFE (C282Y homozygosity)||Interaction with transferrin receptor 1 ||Cirrhosis, diabetes||↑ Transferrin||Phlebotomy|
|Loss of function (AR)||Cardiac failure||↑ Ferritin|
|Increased iron absorption in GI tract||Multisystemic||DNA testing|
|Hemochromatosis (juvenile)||TfR2: Transferrin receptor 2 (AR)||Uptake of iron-bound transferring||Multisystemic iron overload||DNA testing||Phlebotomy|
|HAMP: Hepcidin antimicrobial peptide (AR)|
|Increased iron efflux|
|HJV: Hemojuvelin (AR)||Decreased iron efflux|
|SLC40A (= ferroportine: dominant negative mutations)|
|Aceruloplasminemia (adult)||Ceruloplasmin gene||Brain iron recycling||Adult diabetes||↓ Ceruloplasmin in serum||None|
|Dementia, dystonia||↓ Iron in serum|
|Brain MRI: basal ganglia iron accumulation||↑ Ferritin in serum|
|Neuroferritinopathy (adult)||Light chain of ferritin||Brain iron storage||Early to late adult: dementia, dystonia, dysarthria||↓ Ferritin in serum||None|
|Dominant negative mutations||Normal iron and transferrin|
|Brain MRI: increased iron|
|Neurodegeneration with brain iron accumulation
(NBIA; childhood)||PANK-2 (pantothenate kinase) (AR)||Iron deposit in basal ganglia||Dystonia, behavior problems, neuroaxonal dystrophy,
MRI: “Eye of the tiger” sign (PANK2)||No systemic abnormalities||None|
|PLA2G6 (calcium independent group 6 phospholipase A2)
|Globus pallidus hypointensities|
|GRACILE syndrome (early infantile)16||BCS1L (mitochondrial protein chaperon for
complex III assembly)||Systemic iron overload||Liver injury, hemosiderosis, lactic acidosis,
fetal growth retardation||↑ Ferritin in serum||None|
|Neonatal hemochromatosis (neonatal)||Maternal alloimmunization||Systemic iron deposits||Neonatal ...|
Log In to View More
If you don't have a subscription, please view our individual subscription options below to find out how you can gain access to this content.
Want remote access to your institution's subscription?
Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.
If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.
AccessPediatrics Full Site: One-Year Subscription
Connect to the full suite of AccessPediatrics content and resources including 20+ textbooks such as Rudolph’s Pediatrics and The Pediatric Practice series, high-quality procedural videos, images, and animations, interactive board review, an integrated pediatric drug database, and more.
Pay Per View: Timed Access to all of AccessPediatrics
24 Hour Subscription $34.95
48 Hour Subscription $54.95
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.