McLeod myopathy revisited: more neurogenic and less benign.
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.
Institute of Neuropathology, University Hospital Zürich, Switzerland.
Ekkehard
E
Hewer
Adrian
A
Danek
Benedikt G
BG
Schoser
Marcelo
M
Miranda
Ross
R
Reichard
Claudia
C
Castiglioni
Matthias
M
Oechsner
Hans H
HH
Goebel
Frank L
FL
Heppner
Hans H
HH
Jung
D000328:Adult; D001706:Biopsy; D002819:Chorea / Q000209:etiology; D003402:Creatine Kinase / Q000378:metabolism; D018450:Disease Progression; D005500:Follow-Up Studies; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics; D008297:Male; D001523:Mental Disorders / Q000209:etiology; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000648:ultrastructure; D009154:Mutation; D054546:Neuroacanthocytosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
D007626:Kell Blood-Group System; D003402:Creatine Kinase