Table 2.
Disease causing mutations and clinical phenotypes in 9/21 individuals presenting with rhabdomyolysis.
| Indiv- idual |
Origin | Causative gene (Syndrome name, MOI) |
Nucleotide alteration |
Alteration in coding sequence* |
Zygo -sity |
Conti- nuous AA- sequence Conser- vation |
Presenting symptoms (Age; and CK level [U/L] at presentation) |
Family history of rhabdomyolysis |
Highest creatinine (mg/dL) |
|---|---|---|---|---|---|---|---|---|---|
| ANX | Ashkenazi Jewish | CPT2 (Carnitine palmitoyltransfe- rase II deficiency, AR) | c.338C>T | p.Ser113Leu | Hom | Dm | Muscle cramps, myoglobinuria following exercise (16y; 160,000) | No | 0.9 |
| AN3 | Arab | CPT2 (Carnitine palmitoyltransfe- rase II deficiency, AR) | c.338C>T | p.Ser113Leu | Hom | Dm | Fever and muscle cramps (9y; 130,000) | No | 0.76 |
| AN2 | Ashkenazi Jewish | PFKM (Tarui disease, AR) | c.237+1G>A | splice | Hom | Splice | Fatigue and weakness following exercise (4y; 1,801) Muscle cramps | Sister showed similar clinical and laboratory presentation Parents are healthy. | N/A |
| AN5 | Iranian Jewish | PGAM2 (Glycogen storage disease X, AR) | c.637G>A | p.Gly213Arg | Hom | Dm | following exercise (10y; 2,000) Dark colored | Paternal aunt has rarely muscle weakness. | 0.66 |
| AN7 | Ashkenazi Jewish | RYR1 (Malignant hyperthermia susceptibility 1, AD) | c.179A>G | p.Asp60Gly | Het | Dr | urine and CPK elevation following general anesthesia (46y; 93,000) | No | N/A |
| AN11 | Ashkenazi/Bukharian Jewish | CACNA1S (Malignant hyperthermia susceptibility 5, AD) | c.1678G>T | p.Ala560Ser | Het | Dm | Myalgia, abdominal pain following extreme exercise (20y; 17,974) | No | 1.16 |
| AN13 | Greek Jewish | SCN4A (Hyperkalemic periodic paralysis, type 2, AD) | c.4343G>A | p.Arg1448His | Het | Dr | Abdominal pain, general weakness and fatigue (20y; 870) Myalgia and | Patients’ sibling, father and paternal uncle had elevated CK level following exercise. Maternal | 1.2 |
| AN21 | Ashkenazi Jewish | MYH3 (Freeman- Sheldon syndrome, AD) | c.875C>G | p.Ser292Cys | Het | Dr | paresthesia (15y; 24,000) | grandfather with elevated CK | 0.64 |
| AN20 | Sephardic Jewish | AHCY (Hypermethionin- emia with deficiency of S- Adenosylhomo- cysteine hydrolase, AR) | c.266C>T c.428A>G |
p.Ala89Val p.Tyr143Cys |
Het Het |
Dm Ce | Hypotonia, poor sucking reflex, apneas (2d; 12,353) | No | 0.3 |
*
All mutations had a PolyPhen2 (PP2) humvar score of functional ‘deleteriousness’.
Abbreviations: AA, amino acid; AD, Autosomal dominant; AR, autosomal recessive; CK, creatine kinase; Ce, Caenorhabditis elegans; Dm, Drosophila melanogaster ; Dr, danio rerio; d, day; Het, heterozygous; Hom, homozygous; MOI, mode of inheritance; N/A, not applicable; y, year.