McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients
Abstract
:1. Introduction
2. Material and Methods
2.1. Patients
2.2. Clinical Characterisation
2.3. Laboratory Studies
2.4. Biochemical and Histological Analysis of Muscle Biopsies
2.5. Molecular Genetic Analysis
2.6. Genotype-Phenotype Correlation
3. Results
3.1. Clinical Features
3.2. Laboratory Tests
3.3. Biochemical Features
3.4. Histological Findings
3.5. Molecular Genetic Features
3.6. Genotype–Phenotype Correlation
4. Discussion
4.1. Clinical Features
4.2. Laboratory Findings
4.3. Biochemical Features
4.4. Myohistological and Histochemical Features
4.5. Molecular Genetic Features
4.6. Genotype–Phenotype Correlation
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Patient (Gender) | Genotype | Onset | Family History | Permanent Weakness | Cramps | Masticatory Muscle Involvement |
---|---|---|---|---|---|---|
1 (M) | p.Arg50Ter/p.Arg50Ter | Childhood | − | Thighs | − | − |
2 (M) | p.Arg50Ter/p.Arg50Ter | Childhood | − | Arms, legs | + | − |
3 (F) | p.Arg50Ter/p.Arg50Ter | Childhood | − | Thighs | − | − |
4 (M) | p.Arg50Ter/p.Arg50Ter | Childhood | Brother | Thighs, Arms | − | − |
5 (F) | p.Arg50Ter/p.Arg50Ter | Childhood | − | Legs | − | − |
6 (M) | p.Arg50Ter/p.Arg50Ter | Childhood | − | Arms, legs | − | − |
7 (M) | p.Arg50Ter/p.Arg50Ter | Adolescence | − | Arms, legs | − | − |
8 (M) | p.Arg50Ter/p.Arg50Ter | Late (50 Yrs.) | Cousin | Shoulder, arm | − | − |
9 (M) | p.Arg50Ter/p.Arg50Ter | Late (50 Yrs.) | − | Arms, legs | − | − |
10 (M) | p.Arg50Ter/p.Arg50Ter | Childhood | − | n.a. | − | − |
11 (F) | p.Arg50Ter/p.Arg50Ter | Childhood | Father | n.a. | − | − |
12 (F) | p.Arg50Ter/p.Arg50Ter | Childhood | − | n.a. | − | − |
13 (F) | p.Arg50Ter/p.Arg50Ter | Childhood | − | n.a. | − | − |
14 (F) | p.Arg50Ter/p.Arg50Ter | Childhood | − | n.a. | − | − |
15 (M) | p.Arg50Ter/p.Asp129His | Childhood | − | Thighs, calves | − | − |
16 (F) | p.Arg50Ter/p.Arg139Trp | Childhood | − | Arms, legs, | − | + |
17 (M) | p.Arg50Ter/p.Glu655Lys | Childhood | − | Arms, legs, back | − | − |
18 (F) | p.Arg50Ter/p.Gly686Arg | Childhood | Sister | Arms, legs | − | − |
19 (F) | p.Arg50Ter/p.Gly686Arg | Youth | − | Arms, legs | − | − |
20 (M) | p.Met1Val/p.Met1Val | Adolescence | Several | Shoulders | − | − |
21 (F) | p.Met1Val/p.Met1Val | Youth | − | Arms, legs | − | − |
22 (M) | c.25delG/c.25delG | Youth | Several | Arms, legs | − | − |
23 (F) | p.Tyr85Ter/p.Arg94Trp | Childhood | − | Arms, legs | + | + |
24 (F) | p.Arg94Trp/p.Arg94Trp | Late (63 Yrs.) | − | Thighs, Toe | + | − |
25 (F) | p.Arg270Ter/p.Arg270Ter | Childhood | Brother | Arms, legs | + | − |
26 (M) | IVS6-2A>T/IVS6-2A>T | Childhood | Sister | Shoulders | − | − |
27 (F) | p.Gln337Arg/p.Gln337Arg | Childhood | − | Arms, legs, back | − | − |
28 (F) | p.Tyr574Ter/c.1948delC | Childhood | − | Arms, legs, | − | + |
29 (M) | p.Met680Val/c.2262delA | Childhood | Several | Shoulders | − | − |
Clinical features | Present Study (n = 60) | Other Studies [20,21] (n = 166) | |
---|---|---|---|
n (%) | n (%) | p | |
Exercise intolerance | 60 (100) | 146/166 (89) | n.s. |
Permanent weakness | 28 (47) | 46/166 (28) | 0.02 |
Age at onset (Years) | |||
<15 | 52 (87) | 94/112 (85) | n.s. |
15–30 | 5 (8) | 10/112 (9) | n.s. |
>30 | 3 (5) | 6/112 (6) | n.s |
Age at diagnosis (Years) | |||
<10 | 0 (0) | 5/112 (4) | n.s. |
10–30 | 19 (32) | 55/112 (50) | 0.028 |
30–50 | 32 (53) | 30/112 (27) | <0.001 |
>50 | 9 (15) | 21/112 (19) | n.s. |
Positive family history | 15 (25) | 51/112 (53) | 0.026 |
CK elevation | 33/33 (100) | 54/54 (100) | n.s. |
Second wind | 19/34 (56) | n.a. | - |
No. of Patients | Allele 1 | Allele 2 | Ethnic Origin |
---|---|---|---|
27 | p.Arg50Ter | p.Arg50Ter | Germany (n = 23), UK (n = 4) |
4 | p.Arg50Ter | p.Arg270Ter | Germany (n = 4) |
2 | p.Arg50Ter | p.Gly486Asp | Both Norway |
2 | p.Arg50Ter | p.Gly686Arg | Both Germany |
2 | p.Arg50Ter | c.1239+1G>A* | Both Germany |
2 | p.Met1Val | p.Met1Val | Turkey (n = 1), Lebanon (n = 1) |
1 | p.Arg50Ter | p.Asp129His | Germany |
1 | p.Arg50Ter | p.Arg139Trp | Germany |
1 | p.Arg50Ter | p.Glu655Lys | Germany |
1 | p.Arg50Ter | c2262delA | Germany |
1 | c.25delG | c.25delG | Germany |
1 | c.78_79delTG | c.78_79delTG | Germany |
1 | p.Tyr85Ter | p.Arg94Trp | Germany |
1 | p.Arg94Trp | p.Arg94Trp | UK |
1 | p.Gly157Val | p.Glu349Lys | Germany |
1 | p.Gly205Ser | p. Arg576Ter | Germany |
1 | p.Arg270Ter | p.Glu349Lys | Germany |
1 | p.Arg270Ter | p.Arg270Ter | Italy |
1 | c.772-2A>T* | c.772-2A>T* | Germany |
1 | p.Gln337Arg | p.Gln337Arg | Germany |
1 | p.Glu384Lys | c.1155_1156delGG | Germany |
1 | p.Ser450Leu | p.Ser450Leu | Syria |
1 | p.Leu397Pro | c2262delA | Germany |
1 | p.Arg570Trp | p.Gly686Arg | Austria |
1 | p.Tyr574Ter | c.1948delC | Germany |
1 | p.Gln666Glu | c.2262delA | Germany |
1 | p.Met680Val | c2262delA | Turkey |
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Joshi, P.R.; Deschauer, M.; Zierz, S. McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients. Biomedicines 2020, 8, 33. https://doi.org/10.3390/biomedicines8020033
Joshi PR, Deschauer M, Zierz S. McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients. Biomedicines. 2020; 8(2):33. https://doi.org/10.3390/biomedicines8020033
Chicago/Turabian StyleJoshi, Pushpa Raj, Marcus Deschauer, and Stephan Zierz. 2020. "McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients" Biomedicines 8, no. 2: 33. https://doi.org/10.3390/biomedicines8020033
APA StyleJoshi, P. R., Deschauer, M., & Zierz, S. (2020). McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients. Biomedicines, 8(2), 33. https://doi.org/10.3390/biomedicines8020033