APECED is an acronym for autoimmune
polyendocrinopathy, candidiasis, ectodermal dystrophy. This autoimmune syndrome
is composed of multiple endocrinopathies associated with various other
signs, including hepatitis and eye abnormalities. Can lead to premature death.
Whitaker Syndrome; Autoimmune Polyendocrinopathy
Syndrome, type I; Polyglandular Autoimmune Syndrome Type I;
Hypoadrenocorticism Hypoparathyroidism Moniliasis.
Very rare syndrome. Occurs more frequently in Finland,
where the prevalence in the general population is estimated to be 1:25,000
in the general population. Depending on the source, females are affected up
to twice as often as males.
Autosomal recessive and autosomal dominant
inheritance are observed. This disorder may not be inherited as a simple
mendelian recessive but may be autoimmune in nature.
Maps to 21q22.3. A mutation in the AIRE
(autoimmune regulator) gene is responsible for pathogenesis of APECED
Determined by the presence of two of the three
major clinical symptoms: (1) hypoparathyroidism (present in almost 80% of
patients), (2) corticoadrenal hyperplasia or hypoplasia (>70%), and/or
(3) chronic mucocutaneous candidiasis. It affects children and adults
younger than 35 years and can be lethal in infancy or childhood.
Mucocutaneous candidiasis is most often the first
symptom and usually appears between 3 and 5 years of age. Over the next 5
years, hypoparathyroidism very likely occurs, whereas adrenal insufficiency
often takes another 5 years to become clinically manifest. This is the most
common order and time frame; however, wide variations are possible, and the
different organ manifestations of this disease can occur independent of each
other. More than three fourths of APECED patients develop chronic
hypoparathyroidism, which can lead to tetany with carpopedal spasms
(Trousseau sign), Chvostek sign, acral paresthesias, laryngospasm, mild
encephalopathy, seizures, cataracts, and papilledema. The ECG may show QT
interval prolongation and ventricular arrhythmias. Signs of
mineralocorticoid and glucocorticoid deficiency often occur simultaneously,
although their onsets can be up to 3 years apart. Initial symptoms are
chronic fatigue, weakness, anorexia, and orthostatic hypotension.
Hyperpigmentation as a sign of primary adrenal insufficiency can be helpful
for the differential diagnosis. Weight loss and arterial hypotension (not
only associated with orthostasis) usually are late signs of Addisonian
syndrome. Beside the endocrine features, patients may have hypogonadism
(more frequent in women), insulin-dependent diabetes mellitus,
hypoaldosteronism, and pituitary defects. Other organs affected may include
the eye (keratopathy, keratoconjunctivitis, cataract, photophobia), teeth
(enamel hypoplasia), skin (vitiligo, ectodermal dystrophy, alopecia, chronic
mucocutaneous candidiasis), and gastrointestinal tract (malabsorption,
diarrhea, chronic atrophic gastritis, pernicious anemia, chronic active
hepatitis, cholelithiasis, asplenia). Cerebral vascular anomalies and
intracranial calcifications have been reported. Laboratory investigations
may detect pernicious anemia, multiple autoantibodies, and abnormal
phosphate and calcium metabolism.
Evaluate endocrine status clinically
and with laboratory investigations, including blood and urine electrolytes
(phosphate and calcium), blood glucose, thyroid function tests, and
echocardiography. Obtain a complete blood count (anemia). Evaluate cardiac
status (clinical, ECG). Evaluate hepatic function in case of chronic
hepatitis (clinical, ...