Harderoporphyria is a rare disorder of
heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
biosynthesis, inherited in an
autosomal recessive manner caused by specific mutations in the ''CPOX'' gene. Mutations in ''CPOX'' usually cause
hereditary coproporphyria
Hereditary coproporphyria (HCP) is a disorder of heme biosynthesis, classified as an acute hepatic porphyria. HCP is caused by a deficiency of the enzyme coproporphyrinogen oxidase, coded for by the ''CPOX'' gene, and is inherited in an autosom ...
, an acute hepatic
porphyria
Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...
, however the K404E mutation in a homozygous or compound heterozygous state with a
null allele
A null allele is a nonfunctional allele (a variant of a gene) caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the alle ...
cause the more severe harderoporphyria.
Harderoporphyria is the first known metabolic disorder where the disease
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
depended on the type and location of the mutations in a gene associated with multiple disorders.
In contrast with other porphyrias, which typically present with either cutaneous lesions after exposure to sunlight or acute neurovisceral attack at any age (most commonly in adulthood), harderoporphyria is characterized by
jaundice,
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
enlarged liver and
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . , often presenting in the neonatal period. Later in life, these individuals may present with photosensitivity similar to that found in
cutaneous porphyrias.
Biochemically, harderoporphyria presents with a distinct pattern of increased harderoporphyrin (2-vinyl-4,6,7-tripropionic acid porphyrin)
in
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellular ...
and particularly in
feces, a metabolite that is not seen in significant quantities in any other porphyria.
Enzyme tests show markedly reduced activity of
coproporphyrinogen oxidase, compared to both unaffected individuals and those affected with hereditary coproporphyria, consistent with recessive inheritance.
Harderoporphyria is a rare condition, with less than 10 cases reported worldwide. It may be underdiagnosed, as it does not have the typical presentation associated with a porphyria.
It was identified as a variant type of coproporphyria in 1983, in a family with three children identified at birth with jaundice and hemolytic anemia.
There is no standard treatment for harderoporphyria; care is mainly focused on the management of symptoms.
References
External links
{{Heme metabolism disorders
Porphyrias
Heme metabolism disorders