Neuromuscular Findings in Eight Italian Families with Neuroacanthocytosis

Dotti, Maria Teresa; Malandrini, Alessandro; Federico, Antonio

doi:10.1007/1-4020-2898-9_15

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…The arrows indicate borders between normal sarcolemma and defects. Danek et al, 2001;Dotti et al, 2004). In contrast to the unspecific sural nerve findings from single cases in the literature, however, the samples available here give clear structural evidence of a sensory-motor axonopathy in MLS.…”

Section: Discussioncontrasting

confidence: 80%

“…Previous reports of MLS muscle histology documented a variety of unspecific changes such as type 1 fibre predominance and type 2 fibre atrophy, but also clearly myopathic changes such as increased fibre size variability and increased numbers of centralized nuclei as well as fibre type grouping that is usually considered as a reinnervation phenomenon due to axonal neuropathy (Swash et al, 1983;Witt et al, 1992;Malandrini et al, 1994;Jung et al, 2001b;Dotti et al, 2004). The latter had been previously interpreted as a myopathic finding in resemblance to findings in female carriers of Duchenne muscular dystrophy (Witt et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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McLeod myopathy revisited: more neurogenic and less benign

Hewer

Danek

Schöser

et al. 2007

Brain

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The X-linked McLeod neuroacanthocytosis syndrome (MLS) has originally been denoted as 'benign' McLeod myopathy. We assessed the clinical findings and the muscle pathology in the eponymous index patient, Hugh McLeod, and in nine additional MLS patients. Only one patient had manifested with neuromuscular symptoms. During a mean follow-up of 15 years, however, eight patients including the initial index patient showed elevated skeletal muscle creatine kinase levels ranging from 300 to 3000 U/L, and had developed muscle weakness and atrophy. Two patients had disabling leg weakness. Muscle histology was abnormal in all 10 patients. Clear but unspecific myopathic changes were found in only four patients. All patients, however, had neurogenic changes of variable degree. Post-mortem motor and sensory nerve examinations support the view that muscle atrophy and weakness are predominantly due to an axonal motor neuropathy rather than to a primary myopathy. Multisystem manifestations developed in eight patients at a mean age of 39 years. Three patients manifested with psychiatric features comprising schizophrenia-like psychosis and personality disorder, two presented with generalized seizures and one with chorea. During follow-up, seven patients developed chorea, six had psychiatric disorders, five had cognitive decline and three had generalized seizures. Five patients died because of MLS-related complications including sudden cardiac death, chronic heart failure and pneumonia between 55 and 69 years. In conclusion, our findings confirm that MLS is not a benign condition but rather a progressive multisystem disorder sharing many features with Huntington's disease.

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

McLeod myopathy revisited: more neurogenic and less benign

Hewer

Danek

Schöser

et al. 2007

Brain

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“…Peripheral neuropathy with distal axonopathy and neurogenic muscle atrophy are common but often subclinical findings in ChAc [26].…”

Section: Discussionmentioning

confidence: 99%

Chorea-acanthocytosis in monozygotic twins: clinical findings and neuropathological changes as detected by diffusion tensor imaging, FDG-PET and 123I-β-CIT-SPECT

et al. 2007

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We report on two 33 years old monozygotic twins with chorea-acanthocytosis (ChAc) misdiagnosed as schizophrenia and Tourette syndrome, respectively. Although the patients shared several clinical similarities, there were also some clear differences: twin 1 presented initially with an acute episode of a paranoid schizophrenia, while twin 2 suffered from generalized epileptic seizures. In both twins, MRI demonstrated caudate nucleus atrophy and an increased apparent diffusion coefficient (ADC) in the striatum bilaterally with right sided predominance. (18)F-FDG PET showed bilaterally reduced glucose utilization in the striatum with clearly pronounced reduction on the right side compared to the left and in twin 1 compared to twin 2. Ratios of binding to striatal dopamine transporters (DAT) and serotonin transporters in the hypothalamus midbrain area as determined using (123)I-beta-CIT-SPECT fell within the normal ranges. However, in twin 1 a significant difference in binding to presynaptic DAT with marked reduction on the right hemisphere was observed. Right hemispheric accentuated changes measured by MRI, FDG-PET, and (123)I-beta-CITSPECT correspond to more severe hyperkinetic movements on the left part of the body in both twins. Different neuro-psychiatric features in this monocygotic twin pair suggest that not only genetic but also environmental factors contribute to the clinical symptomatology. Our findings suggest that the main neuropathological process in ChAc is located in the striatum, involving microstructural alterations, and disturbance of metabolism and dopaminergic neurotransmission.

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“…The high levels of transaminases (ALT/AST) and LDH, mentioned in relation to hepatomegaly, might alternatively originate from muscle affection. MLS may be considered a primary myopathy [56]. As sensory and motor axonal polyneuropathy is very common [1,23,39,57], muscle atrophy and weakness have thus been interpreted predominantly due to motor neuropathy [3].…”

Section: Nonhematological Manifestations Of Mlsmentioning

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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Neuromuscular Findings in Eight Italian Families with Neuroacanthocytosis

Cited by 6 publications

References 20 publications

McLeod myopathy revisited: more neurogenic and less benign

McLeod myopathy revisited: more neurogenic and less benign

Chorea-acanthocytosis in monozygotic twins: clinical findings and neuropathological changes as detected by diffusion tensor imaging, FDG-PET and 123I-β-CIT-SPECT

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

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