McArdle's disease in two generations

Schmidt, B J; Servidei, Serenella; Gabbai, Alberto A.; Silva, A. C.; Oliveira, Abílio; DiMauro, Salvatore

doi:10.1212/wnl.37.9.1558

Cited by 44 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Manifesting heterozygotes have been reported in the literature (Table 3), even before the genetics of the disease were known (Fattah et al 1970;Baksi et al 1977;Engel et al 1987;Schmidt et al 1987;Taylor et al 1987;Papadimitriou et al 1990;Manfredi et al 1993). Their symptoms were essentially triggered by exercise and included myalgia, cramps, early fatigue, and weakness, which is in accordance with our data (Table 3).…”

Section: Discussionsupporting

confidence: 91%

“…The pattern of inheritance of this disease is autosomal recessive, although some cases of patients showing McArdle-like symptoms or signs despite having a pathogenic mutation in only one of the two PYGM alleles, the so-called manifesting heterozygotes, have been reported in the literature (Fattah et al 1970;Baksi et al 1977;Engel et al 1987;Schmidt et al 1987;Taylor et al 1987;Papadimitriou et al 1990;Manfredi et al 1993). In some studies, pseudo-dominant inheritance has been established (Chui and Munsat 1976;Wu et al 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Manifesting heterozygotes in McArdle disease: a myth or a reality—role of statins

Núñez-Manchón

Ballester-Lopez

Koehorst

et al. 2018

J of Inher Metab Disea

View full text Add to dashboard Cite

McArdle disease is an autosomal recessive condition caused by deficiency of the PYGM gene-encoded muscle isoform of glycogen phosphorylase. Some cases of "manifesting" heterozygotes or carriers (i.e., patients who show some McArdle-like symptoms or signs despite being carriers of only one mutated PYGM allele) have been reported in the literature but there is controversy, with misdiagnosis being a possibility. The purpose of our study was to determine if there are actually "manifesting" heterozygotes of McArdle disease and, if existing, whether statin treatment can trigger such condition. Eighty-one relatives of McArdle patients (among a total of 16 different families) were studied. We determined whether they were carriers of PYGM mutations and also collected information on exercise tests (second wind and modified Wingate anaerobic test) and statin intake. We found 50 carriers and 31 non-carriers of PYGM mutations. Although we found existence of heterozygotes manifesting some exercise-related muscle problems such as exacerbated myalgia or weakness, they only accounted for 14% of the carriers and muscle symptoms were milder than those commonly reported in patients. Further, no carrier (whether reporting symptoms or not) showed the second wind phenomenon or a flat blood lactate response to maximal-intensity exercise, both of which are hallmarks of McArdle disease. On the other hand, statin myotoxicity was not associated with muscle symptom onset.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Manifesting heterozygotes in McArdle disease: a myth or a reality—role of statins

Núñez-Manchón

Ballester-Lopez

Koehorst

et al. 2018

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…9 Our data confirm that the mutation at codon 49 is the most common genetic defect associated with myophosphorylase deficiency, at least in the American population. However, when residual activity falls below a certain level, approximately 20% of normal, symptoms may become evident.…”

supporting

confidence: 82%

Diagnosis of McArdle's disease by molecular genetic analysis of blood

El-Schahawi¹,

Tsujino²,

Shanske³

et al. 1996

Neurology

View full text Add to dashboard Cite

We analyzed leukocyte DNA from 32 patients with suspected McArdle's disease, 24 of whom had biochemically or histochemically proven myophosphorylase deficiency. We found that 19 were homozygous for the most common mutation at codon 49, 2 were compound heterozygotes, and 1 was a manifesting heterozygote. In six patients, we could find only one mutant allele, suggesting a still unidentified mutation on the second allele. We were unable to identify any of the known mutations in four patients. Our findings indicate that the diagnosis of McArdle's disease can be established in approximately 90% of patients using DNA isolated from leukocytes, thereby avoiding muscle biopsy.

show abstract

“…The occurrence of manifesting heterozygotes with McArdle disease has been a long lasting controversy that could have important implications in diagnosis and genetic counselling 17 – 19. Andersen et al 19 showed that non-symptomatic heterozygotes for PYGM gene mutations had maximal oxidative capacities and peak lactate responses identical to control subjects, suggesting that they are not prone to develop symptoms of McArdle disease.…”

Section: Discussionmentioning

confidence: 99%