Clinical Guidance

Data presently available are insufficient to draw conclusions about genotype-phenotype correlations in McLeod neuroacanthocytosis syndrome . MLS shows considerable phenotypic variability, even among family members with identical XK variants . Only three pathogenic XK missense variants have a possible genotype-phenotype correlation. Although rare, they are potentially useful in the elucidation of structural and functional relationships. For more details see .

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Penetrance

In males, the penetrance of neurologic and neuromuscular manifestations of MLS is high – perhaps even complete – after age 50 years. Available data indicate that most males with the McLeod blood group phenotype will develop clinical manifestations of McLeod neuroacanthocytosis syndrome [, , , ]. In a few individuals, however, neurologic and neuromuscular manifestations may be absent or only minor even after long-term follow up . See . In the past, many reports (including that of the index case) described only hematologic findings, and no neurologic or neuroimaging workup was performed in these individuals [, , , ]. However, in many of these individuals neurologic manifestations were identified during long-term follow up .

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Diagnostic Criteria

Suggestive Findings

The diagnosis of McLeod neuroacanthocytosis syndrome (MLS) should be suspected/considered in an individual with the following clinical and laboratory findings and family history.

CNS Manifestations

Clinical findings

• Progressive chorea syndrome, which also can be part of a clinical triad of movement disorders, cognitive alterations, and psychiatric symptoms ("Huntington-like syndrome")

• Seizures, mostly generalized

Neuroimaging studies

• Males

• Brain CT and MRI may demonstrate variable atrophy of the caudate nucleus and putamen .

• Brain MRI in two males demonstrated extended T2-weighted hyperintense white matter alterations .

• Males and females. Neuroimaging findings may be normal early in the disease course in affected males and in asymptomatic heterozygous females .

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Differential Diagnosis

The two disorders of primary interest in the differential diagnosis of McLeod neuroacanthocytosis syndrome (MLS) are chorea-acanthocytosis and Huntington disease. These disorders – which may appear clinically indistinguishable from MLS – and other disorders in the differential diagnosis of MLS are summarized in .

Table 2.

Genes of Interest in the Differential Diagnosis of McLeod Neuroacanthocytosis Syndrome (MLS)

Gene | Disorder | MOI | Clinical Features of Differential Diagnosis Disorder

Overlapping w/MLS | Distinguishing from MLS

HTT | Huntington disease | AD | • May appear indistinguishable from MLS

• Progressive choreatic mvmt disorder

• Cognitive psychiatric disturbances

| • Anticipation

• Absence of acanthocytes, seizures, myopathy, cardiomyopathy

• Normal CK

VPS13A

| Chorea-acanthocytosis | AR | • Pr...

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with McLeod neuroacanthocytosis syndrome (MLS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with McLeod Neuroacanthocytosis Syndrome

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Clinical Guidance

Blood transfusions with Kx antigens should be avoided in males with the McLeod blood group phenotype. Kx-negative blood or, if possible, banked autologous or homologous blood should be used for transfusions. Note that because heterozygous females have both Kx+ and Kx- red blood cells, they can be transfused with Kx+ homologous blood products.

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with McLeod Neuroacanthocytosis Syndrome

Source: GeneReviews — "McLeod Neuroacanthocytosis Syndrome"