Disorders of metal metabolism and transport
Autosomal recessive (1/30,000
births); due to mutation in the ATP7B
gene that encodes for a cell membrane ATP-sensitive copper pump. The con-dition
results in a build-up of intracellular hepatic copper with subsequent hepatic
dysfunction, neurological abnormalities, and haemolytic anaemia.
Usually develop from the age of
10yrs onwards (rare <5yrs). Half of patients first present with chronic
active hepatitis (which may lead to cir-rhosis), and half with neurological
symptoms including mood disorder, psychosis, and features consistent with
Parkinson’s disease. Haemolysis is usually present only in severe cases. Other
features seen include renal tubular acidosis, renal stones, and cardiomyopathy.
•
Low
plasma concentrations of caeruloplasmin (in 80% of patients). Elevated 24hr
urinary copper excretion.
•
Ophthalmoscopy
to detect Kayser–Fleischer rings (although their absence does not rule out
Wilson disease).
•
Lifelong
chelating agents (e.g. D-penicillamine).
•
Liver
transplantation may be needed in severe disease.
X-linked recessive. Caused by
mutation in the gene encoding Cu2+-transporting ATPase, alpha
polypeptide. The disease is characterized by:
•
early
onset growth retardation;
•
peculiar
hair development (sparse, steely, or kinky hair);
•
focal
cerebral and cerebellar degeneration.
The phenotype also includes
hypotonia, seizures, microcephaly, and oste-oporosis. Predisposition to
intracranial haemorrhage is also recognized.
Biochemical analysis reveals low
plasma levels of caeruloplasmin and copper.
At least 4 inherited iron-overload
disorders have been identified:
•
Classic haemochromatosis (HFE 1): autosomal recessive affecting 1 in 200 to 1 in 400 of population. Caused
by mutation in either HFE gene (on
6p21.3) or haemojuvelin gene (HJV)
(1q21).
•
Juvenile haemochromatosis (HFE 2):
AR.
•
Haemochromatosis type 3 (HFE 3): AR.
•
Haemochromatosis type 4 (HFE4): AD.
The clinical features of haemochromatosis
are wide ranging and include:
·hepatomegaly;
•
Splenomegaly.
•
Cirrhosis
of the liver.
•
Hypermelanotic
pigmentation of the skin.
•
Heart
failure (cardiomyopathy).
•
Joint
stiffness and arthritis.
•
Involvement of the endocrine
glands: can lead to
diabetes mellitus, adrenal
insufficiency, gonadal failure, and hypopituitarism.
•
Increased
susceptibility to certain infections is recognized (e.g. Salmonella, Klebsiella).
Primary hepatocellular carcinoma
complicating cirrhosis is responsible for about one-third of deaths in affected
homozygotes.
Increased serum iron and ferritin
levels. Liver biopsy.
Repeated therapeutic phlebotomy.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.