Minerals and Trace Elements 199● by phosphorylation, and hence activation of many
catalytic proteins.
As phosphorus is not irreversibly consumed in these
processes and can be recycled indefi nitely, the actual
functions of dietary phosphorus are fi rst to support
tissue growth (either during individual development
or through pregnancy and lactation), and second to
replace excretory and dermal levels. In both processes,
it is necessary to maintain a normal level of inorganic
phosphate in the ECF, which would otherwise be
depleted of phosphorus by growth and excretion.
Defi ciency symptoms
Inadequate phosphorus intake is expressed as hypo-
phosphatemia. Only limited quantities of phosphate
are stored within cells, and most tissues depend on
ECF inorganic phosphate for their metabolic phos-
phate. When ECF inorganic phosphate levels are
low, cellular dysfunction follows. At a whole organ-
ism level, the effects of hypophosphatemia include
anorexia, anemia, muscle weakness, bone pain, rickets
and osteomalacia, general debility, increased suscep-
tibility to infection, paresthesia, ataxia, confusion, and
even death. The skeleton will exhibit either rickets in
children or osteomalacia in adults. In both groups,
the disorder consists of a failure to mineralize forming
growth plate cartilage or bone matrix, together with
impairment of chrondroblast and osteoblast func-
tion. These severe manifestations are usually confi ned
to situations in which ECF phosphate falls below
approximately 0.3 mmol/l. Phosphorus is so ubiqui-
tous in various foods that near total starvation is
required to produce dietary phosphorus defi ciency.
Toxicity
Serum inorganic phosphate rises as total phosphorus
intake increases. Excess phosphorus intake from any
source is expressed as hyperphosphatemia and, essen-
tially, all the adverse effects of phosphorus excess are
owing to the elevated inorganic phosphate in the ECF.
The principal effects that have been attributed to
hyperphosphatemia are:
● adjustments in the hormonal control system regu-
lating the calcium economy
● ectopic (metastatic) calcifi cation, particularly of the
kidney
● in some animal models, increased porosity of the
skeleton
● a suggestion that high phosphorus intakes could
decrease calcium absorption by complexing calcium
in the chyme.
Concern about high phosphorus intake has been
raised in recent years because of a probable popula-
tion level increase in phosphorus intake through
such sources as cola beverages and food phosphate
additives.Genetic diseases
Several disease states are associated with phosphorus
defi ciency, some of which have genetic roots, for
example X-linked hypophosphatemia, hypophospha-
temic bone disease, and Fanconi’s syndrome.
X-linked hypophosphatemia is, as the name implies,
inherited as an X-linked dominant trait with the
mutant gene located in Xp22.2–p.22.1. The classical
triad, fully expressed in hemizygous male patients,
consists of:● hypophosphatemia
● lower limb deformities
● stunted growth rate.Although low serum phosphate is evident early after
birth, it is only at the time of weight bearing that
leg deformities and progressive departure from the
normal growth rate become suffi ciently striking to
attract attention and make parents seek medical
opinion. It is generally accepted that hypophosphate-
mia is the consequence of a primary inborn error of
phosphate transport, probably located in the proxi-
mal nephron.
Hypophosphatemic bone disease is characterized
clinically by modest shortening of stature, bowing of
the lower limbs, and nonrachitic bone changes (some-
what resembling metaphyseal chondrodysplasia)
and biochemically by hypophosphatemia. Although a
defect in renal transport of phosphate was demon-
strated, the defect appeared to be different from that
of X-linked hypophosphatemia.
Fanconi’s syndrome is an autosomal dominant dis-
order. It is characterized by lactic aciduria and tubular
proteinuria in childhood, with glycosuria and amino-
aciduria developing in the second decade and osteo-
malacia from the start of the fourth decade. Glomerular
function deteriorates slowly but is compatible with a
normal lifespan. There has been reported linkage of
the disorder to chromosome 15q15.3.