Keywords
LPIN1, rhabdomyolysis, myoglobinurea, renal insufficiency, genetics
LPIN1, rhabdomyolysis, myoglobinurea, renal insufficiency, genetics
In a recent article, Yim et al. reported a 15-month-old male who experienced severe rhabdomyolysis with a creatine-kinase value (CKV) of 127494 U/l one day after intramuscular injection of an unidentified drug by the general practitioner (GP)1. Rhabdomyolysis was not attributed to this injection but to compound heterozygous variants in LPIN11. Each of the parents carried one of these variants but was clinically unaffected1. This correspondence article provides reasonings as to why the detection of heterozygous variants in LPIN1 does not necessarily imply pathogenicity in this case.
Rhabdomyolysis may not only occur in mitochondrial disorders (beta-oxidation defects are mitochondrial disorders) and glycogenoses, but more frequently in response to drugs or toxins2. Thus, it is crucial to find out which drug the GP injected one day prior to admission, not only to identify the compound, but also to ensure that other patients were not exposed to any hazardous risks due to a possibly toxic drug.
Since the variant c.1949_1967dupGTGTCACCACGCAGTACCA was classified as likely pathogenic, the variant c.2410G>C as a variant of unknown significance, and since one parent each carried one of either variants, it is conceivable that the parent who carried the variant c.1949_1967dupGTGTCACCACGCAGTACCA also had experienced muscle manifestations previously. However, the family history is described as negative for rhabdomyolysis, malignant hyperthermia, or neuromuscular disorders making the pathogenicity of this variant quite unlikely. However, an extended family history should also be taken from the grandparents from the mother’s and father’s side to assess if they ever experienced any muscle symptoms.
Since LPIN1 variants have been previously reported in association with recurrent rhabdomyolysis3,4, it is quite likely that the index patient or one of the parents had elevated CKVs. Thus, the records of the index patient or the parent who carried the likely pathogenic LPIN1 variant should be checked to see if these individuals ever showed elevated CKVs. Of particular interest are CKVs after birth, exercise, infection, anaesthesia, or application of drugs. This is because CKV may particularly increase with these conditions. Since the younger sister of the index patient also carried the compound heterozygous LPIN1 variants, we should be informed about the course of the mother’s pregnancy with this younger child, about the sister’s CKVs at birth and later, and further follow-up, including genetic counselling.
In the case report1, the patient has a second episode of rhabdomyolysis at the age of six years. Current medication the index patient was taking at the time of this second episode should be examined, and also if the cause could have been triggered by exercise5. A male of 6 years of age most likely is lively and usually highly physically active.
Overall, this interesting case report has some limitations, which should be addressed before attributing rhabdomyolysis to the LPIN1 variants. Triggers of rhabdomyolysis should be unequivocally identified, a more extensive family history taken, and previous CKVs provided. Functional and biochemical tests should be carried out to confirm or exclude pathogenicity attributed to LPIN1 variants.
No data is associated with this article.
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Is the rationale for commenting on the previous publication clearly described?
Yes
Are any opinions stated well-argued, clear and cogent?
Yes
Are arguments sufficiently supported by evidence from the published literature or by new data and results?
Yes
Is the conclusion balanced and justified on the basis of the presented arguments?
Yes
References
1. Quinlivan R, Jungbluth H: Myopathic causes of exercise intolerance with rhabdomyolysis.Dev Med Child Neurol. 2012; 54 (10): 886-91 PubMed Abstract | Publisher Full TextCompeting Interests: No competing interests were disclosed.
Reviewer Expertise: Inherited muscular disorders, mitochondrial diseases, rhabdomyolysis.
Is the rationale for commenting on the previous publication clearly described?
Yes
Are any opinions stated well-argued, clear and cogent?
Yes
Are arguments sufficiently supported by evidence from the published literature or by new data and results?
Yes
Is the conclusion balanced and justified on the basis of the presented arguments?
Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Meuromuscular disordres, mitochondrial myopathy, Rhabdomyolysis
Is the rationale for commenting on the previous publication clearly described?
Yes
Are any opinions stated well-argued, clear and cogent?
Yes
Are arguments sufficiently supported by evidence from the published literature or by new data and results?
Yes
Is the conclusion balanced and justified on the basis of the presented arguments?
Yes
References
1. Zhang P, Verity MA, Reue K: Lipin-1 regulates autophagy clearance and intersects with statin drug effects in skeletal muscle.Cell Metab. 2014; 20 (2): 267-79 PubMed Abstract | Publisher Full TextCompeting Interests: No competing interests were disclosed.
Reviewer Expertise: Inherited Metabolic Diseases
Is the rationale for commenting on the previous publication clearly described?
Yes
Are any opinions stated well-argued, clear and cogent?
Yes
Are arguments sufficiently supported by evidence from the published literature or by new data and results?
Yes
Is the conclusion balanced and justified on the basis of the presented arguments?
Yes
References
1. Scalco RS, Gardiner AR, Pitceathly RD, Zanoteli E, et al.: Rhabdomyolysis: a genetic perspective.Orphanet J Rare Dis. 2015; 10: 51 PubMed Abstract | Publisher Full TextCompeting Interests: No competing interests were disclosed.
Reviewer Expertise: Minor revision is advised without the need to return the article to me.
Alongside their report, reviewers assign a status to the article:
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Version 1 13 Jan 20 |
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