Acanthocytosis Clinical Presentation

Updated: Mar 24, 2021
  • Author: Pedro A de Alarcon, MD; Chief Editor: Hassan M Yaish, MD  more...
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Patients with acanthocytosis may have a history of chronic diarrhea with pale, foul-smelling, and bulky stools; loss of appetite and vomiting; and slow weight gain and decreased growth, possibly with a bleeding tendency. Patients may report symptoms of ataxia, tremors, visual abnormalities, jaundice, abdominal pain, pallor, dark urine, and recurrent infections. Adolescents and adults may report dyskinesias, specifically orolingual, and cognitive deterioration.



Hematologic findings include the following:

Ocular findings include the following:

  • Progressive retinitis pigmentosa with loss of night vision, visual acuity, and color vision

  • Nystagmus after age 10 years

  • Ophthalmoplegia with strabismus

  • Progressive exotropia

  • Cataracts

GI findings include the following:

Neurologic findings include the following:

  • Loss of deep tendon reflexes

  • Decreased sensation to touch, pain, temperature, and position

  • Stocking-glove distribution of hypoesthesia

  • Decreased muscle strength

  • Intention tremors and progressive ataxia with clumsiness and gait disturbances, dysarthria, dysdiadochokinesis, and dysmetria

  • Chorea

  • Mental retardation, cognitive decline, neuropsychological abnormalities

  • Altered mental status

  • Fatigue

  • Cold intolerance

Skin palmar erythema findings include the following:

  • Spider angiomas

  • Abdominal wall collateral veins

  • Edema

  • Recurrent skin infections

Skeletomuscular findings include the following:

  • Muscular atrophy

  • Muscle contractures

  • Kyphoscoliosis

  • Pes cavus

  • Pes equinovarus



Autosomal recessive abetalipoproteinemia

Heterozygotes are usually healthy. Disease arises from homozygosity in affected alleles. Underlying mutations in the microsomal triglyceride transfer protein (MTP) gene cause a congenital absence of beta-apolipoprotein in the plasma, as well as decreased levels of cholesterol, very–low-density lipoprotein (VLDL), and low-density lipoprotein (LDL). Multiple mutations have been described in the MTP gene, which is localized on chromosome 4. These mutations result in a lack of functional MTP complex. MTP catalyzes the transport of triglyceride, cholesterol ester, and phospholipids between phospholipid surfaces and is required for secretion of ApoB-containing lipoproteins. [9, 10]

Homozygous autosomal dominant familial hypobetalipoproteinemia

This rare condition is caused by various APOB gene mutations. [11] APOB is located on chromosome 2, and various mutations have been described. This disorder has clinical features similar to abetalipoproteinemia but has milder phenotypes. The synthesis of hepatocyte beta-apoprotein is reduced because of low RNA transcription. LDLs in plasma are decreased.


This term describes a group of phenotypically and genotypically heterogeneous disorders with acanthocytosis and onset of neurologic symptoms in adolescence or adulthood. Acanthocytosis has a variable percentage and is a diagnostic hallmark. Plasma lipoproteins are normal.

Genetic studies distinguish certain entities, of which the core syndromes are autosomal recessive chorea-acanthocytosis (VPS13A mutation on chromosome 9q21, which encodes for chorein), [12, 13, 14, 15] X-linked McLeod syndrome (XK mutation, which encodes for Kx), [16, 17] pantothenate kinase–associated neurodegeneration (PANK2 mutation on chromosome 20p13), and Huntington disease–like 2 (JPH3 mutation on chromosome 16q24).

In chorea-acanthocytosis the primary cerebral damage is found in the caudate nucleus, putamen, and pallidum, which have significant atrophy with loss of neurons and gliosis. Chorein abnormalities of skeletal muscles might be associated with primary involvement of skeletal muscle. A study by Lupo et al indicated that in patients with chorea-acanthocytosis, autophagy in the red blood cells is impaired, with this impairment related to the cytoplasmic accumulation of active Lyn, a tyrosine kinase. [18]

Patients who develop McLeod syndrome carry the McLeod blood group, which lacks the Kx antigen, a membrane precursor of the Kell antigen. [19]

A study by Peikert et al indicated that the serum neurofilament light-chain concentration is higher in patients with chorea-acanthocytosis, as well as in persons with McLeod syndrome, than in healthy controls; levels were 18.73 pg/mL in the report’s chorea-acanthocytosis cohort, and 7.37 pg/mL and 3.10 pg/mL in the two control cohorts. According to the investigators, this concentration increase seems to be a product of peripheral and central nervous system neuroaxonal damage. [20]

In(Lu) Lu(a-b-) red cell phenotype

This null Lutheran blood group phenotype is caused by inhibition of antigen expression by In(Lu), the inherited, dominantly acting inhibitor. Red cells are abnormally shaped, but no hemolysis is present.

Idiopathic neonatal hepatitis

This may manifest as acanthocytosis and hemolytic anemia, which can be severe. The process resolves after several months in approximately 65% of cases. Cirrhosis occurs in 20% of cases, and hepatocellular necrosis and death can occur in 10-20% of cases.

Infantile pyknocytosis

Patients with this benign transient process present during the first few days of life with jaundice, mild hepatosplenomegaly, and moderately severe hemolytic anemia. As many as 50% of RBCs may be pyknotic and resemble acanthocytes. Reticulocytes range from 10-20% and are not pyknotic. Transfused RBCs acquire the same pyknotic morphology and are prematurely destroyed, indicating extrinsic causation. The causative mechanisms are unclear. The condition resolves within a mean of 4 months.

Anorexia nervosa, cystic fibrosis, celiac disease, and severe malnutrition

The mechanism of causation is unclear. Fat malabsorption or insufficient intake and vitamin E deficiency contribute. An abetalipoproteinemialike lipid profile has been described. The morphologic abnormality is reversed with improved nutrition.


Acanthocytes are found in 20-65% of patients with a frequency rate of 0.5-2%. Evidence of acanthocytes in adults suggests hypothyroidism in as many as 90% of cases.

Myxedema and panhypopituitarism

RBC lipids are normal, and the cell morphology normalizes with appropriate therapy.Severe liver dysfunction due to alcoholic cirrhosis, metastatic liver disease, hemochromatosis, neonatal hepatitis, cholestasis, Wilson disease, severe acute hepatitis, and infantile pyknocytosis

Other causes

The following may also be observed:

  • Transient hemolysis associated with fatty metamorphosis of the liver and hypoglycemia (Zieve syndrome)

  • Transient hemolysis and stomatocytosis in alcoholism

  • Mild hemolysis and spherocytosis observed in individuals with congestive splenomegaly