Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series

Lhomme, Faustine; Peyrard, Thierry; Babinet, Jérôme; Abou-Chahla, Wadih; Durieu, I.; Moshous, Despina; Neven, Bénédicte; Rohrlich, Pierre‐Simon; Albinni, Souha; Amiranoff, Denise; Dumont, M; Lortholary, Olivier; Héritier, Sébastien; Marguet, Christophe; Suarez, Félipe; Fischer, Alain; Blanche, Stéphane; Hermine, Olivier; Mahlaoui, Nizar

doi:10.1007/s10875-020-00791-w

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…Deletions or partial deletions of the two genes thus lead to a contiguous gene deletion syndrome that combines MLS with chronic granulomatous disease (OMIM #306400). As the latter often requires blood transfusion [18], MLS ought to be ruled out in chronic granulomatous disease patients prior to allogenic transfusions in order to avoid alloimmunization and subsequent posttransfusion complications [19]. Larger deletions of the Xp21 region may additionally involve genes associated with Duchenne muscular dystrophy (OMIM #310200), retinitis pigmentosa (OMIM #300029) and ornithine transcarbamylase deficiency (OMIM #311250), respectively [1].…”

Section: Xk and Vps13a Genes Mode Of Inheritancementioning

confidence: 99%

XK-Associated McLeod Syndrome: Nonhematological Manifestations and Relation to VPS13A Disease

Peikert

Hermann

Danek³

2022

Transfus Med Hemother

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Background: McLeod syndrome (MLS) is an X-linked multisystemic progressive disorder caused by loss of function mutations in the XK gene. The rare blood group phenotype of MLS patients with absent Kx antigen requires the support of specialized transfusion institutions because of the risk of transfusion complications. Acanthocytosis of red blood cells occurs in almost all patients. Nonhematological manifestations of MLS are very similar to those of VPS13A disease (chorea-acanthocytosis), an autosomal-recessive condition. Their shared phenotype apart from acanthocytosis includes movement disorders such as chorea and dystonia, epilepsy, peripheral neuropathy, and muscle involvement, typically with creatine kinase (CK) elevation, cardiomyopathy included. Summary: In this review, we describe the nonhematological manifestations of MLS in comparison with those of VPS13A disease. While there are many similarities, differences such as mode of inheritance, sex distribution, age at manifestation, severity of heart involvement, frequency of feeding dystonia or of involuntary head drops may help to distinguish these disorders in the clinic. Immunohematological demonstration of the McLeod-Kell phenotype or detection of pathogenic mutations of XK (or VPS13A, respectively) is the gold standard for distinction. “Neuroacanthocytosis” was often used as an overarching term, but is potentially misleading, as the term does not refer to a defined disease entity. Its use, if continued, must not prevent clinicians to seek a final diagnosis on the basis of molecular findings. The clinical similarity of MLS and VPS13A disease has long suggested some shared pathophysiology. Evidence for molecular interaction between XK, the McLeod protein, and chorein, the VPS13A gene product, has recently been put forward: XK forms a complex with chorein/VPS13A, a bulk lipid transporter located at various membrane contact sites. The exact role of XK in this complex needs to be further elucidated. Impairment of bulk lipid transport appears as the common denominator of both MLS and VPS13A disease. A variety of further conditions may in time be added to the “bulk lipid transport diseases,” such as the recently recognized disorders caused by mutations in the VPS13B, VPS13C, and VPS13D genes. Key Messages: (1) Patients diagnosed with the rare red cell McLeod phenotype (McLeod syndrome, MLS) require interdisciplinary collaboration of transfusion medicine specialists, neurologists, and cardiologists for both their hematological and nonhematological disease manifestations. (2) The phenotypical similarity of MLS and VPS13A disease, often leading to either confusion or insufficient diagnostic depth (under the label of “neuroacanthocytosis”), is based on interaction of the respective proteins, XK and chorein, within the cellular machinery for bulk lipid transport. (3) Overall, the term “bulk lipid transport diseases” seems useful for further research on a group of conditions that may not only share pathophysiology, but may also share treatment approaches.

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Section: Xk and Vps13a Genes Mode Of Inheritancementioning

confidence: 99%

XK-Associated McLeod Syndrome: Nonhematological Manifestations and Relation to VPS13A Disease

Peikert

Hermann

Danek³

2022

Transfus Med Hemother

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“…Importantly, XK null and missense mutations can cause the McLeod syndrome which is associated with acanthocytes, a late onset of neurological impairment, chorea‐like disease, cardiomyopathy, and various degrees of muscular atrophy 1,3 . Large deletions in the X chromosome can also cause McLeod syndrome, X‐linked Chronic Granulomatous Disorder, and the contiguous gene deletion syndrome 4,5 . Here, we report the molecular basis of the McLeod phenotype in a healthy male blood donor found by random screening for depressed Kell expression, a patient referred for a family history of a McLeod phenotype, and a patient referred for testing as part of a neurological workup.…”

Section: Introductionmentioning

confidence: 92%

Three new XK alleles; two associated with a McLeod RBC phenotype

et al. 2021

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“…It is important to note, however, that not all patients with CGD have the McLeod phenotype and vice versa 7 . A French national database, describing 26 patients with the McLeod phenotype, only identified eight with concurrent CGD 7 . Individual detailed case reports of the McLeod phenotype without CGD also exist 8,9 …”

Section: Understanding the Diagnosis Of Mcleod Phenotypementioning

confidence: 99%

How we approach transfusions in a patient with high risk of alloimmunization from McLeod phenotype

Addams

Hasan

Saifee

2022

Pediatric Blood & Cancer

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McLeod phenotype-caused by the missing Xk protein-is a very rare red cell phenotype, one characteristic of McLeod syndrome, and sometimes associated with X-linked chronic granulomatous disease (CGD). Diagnosis of McLeod phenotype is important for appropriate transfusion management, because red blood cells from all healthy donors will have the Xk protein with its Kx antigen and can lead to red cell antibody formation without the ability to find compatible McLeod phenotype blood for transfusion. We offer a review and approach to diagnosis of the McLeod phenotype and special transfusion considerations.

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Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series

Cited by 11 publications

References 30 publications

XK-Associated McLeod Syndrome: Nonhematological Manifestations and Relation to VPS13A Disease

XK-Associated McLeod Syndrome: Nonhematological Manifestations and Relation to VPS13A Disease

Three new XK alleles; two associated with a McLeod RBC phenotype

How we approach transfusions in a patient with high risk of alloimmunization from McLeod phenotype

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