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Causas metabólicas de rabdomiólise associadas a mutações no gene LPIN1
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Advisor(s)
Abstract(s)
A rabdomiólise resulta da lise do músculo-esquelético, devido à lesão no
tecido muscular com consequente libertação de componentes intracelulares
do músculo para a corrente sanguínea, originando mioglobinúria e,
nos casos mais graves, falência renal aguda. As causas mais frequentes
de rabdomiólise são o consumo de álcool, drogas, exercício físico intenso,
compressão muscular traumática e infeções. As miopatias metabólicas
são causas de rabdomiólise e decorrem da incapacidade em produzir
a quantidade de ATP adequada às necessidades das células musculares,
por deficiência de enzimas do metabolismo dos glícidos, lípidos ou
nucleósidos. Normalmente surgem na infância, sob a forma de fraqueza
muscular e mioglobinúria recorrentes após exposição a estímulos que
em condições normais não causam necrose muscular, como é o caso do
exercício físico ligeiro, infeções virais ou jejum prolongado. Estas doenças
são normalmente causadas por defeitos na -oxidação mitocondrial dos
ácidos gordos, no entanto alterações no metabolismo da Lipina constituem
a segunda causa mais comum de rabdomiólise com início precoce.
Esta deficiência é autossómica recessiva e está associada a mutações
no gene LPIN1. Neste sentido foi implementado este estudo genético na
nossa Unidade, o que permitiu a identificação do primeiro doente português
com uma nova mutação no gene LPIN1. Este estudo contribuiu para
esclarecer a causa da doença nesta família, expandir o espectro mutacional
deste gene, assim como oferecer um aconselhamento genético e
diagnóstico pré-natal às famílias afetadas. Os nossos dados corroboram
assim a importância do estudo molecular do gene LPIN1 para confirmar
doentes (crianças e adultos) com rabdomiólise recorrente. A caraterização
molecular destes doentes é importante uma vez que existe a possibilidade
de um tratamento adequado.
Rhabdomyolysis results from damage in skeletal muscle fibres and release of intracellular components of the muscle to the bloodstream, which leads to myoglobinuria, and in severe cases, acute renal failure. The most frequent causes of rhabdomyolysis are alcohol and other drugs consumption, excessive physical activity, trauma and infections. As metabolic myopathies are causes of rhabdomyolysis and result from the inability to produce an adequate amount of ATP for muscle needs, due to enzymatic deficiencies in carbohydrates, lipids or nucleosides metabolism. Usually occur in childhood and are expressed by pain, muscle weakness and myoglobinuria after physical exercise, viral infections or fasting, which under normal conditions do not cause muscle necrosis. These diseases are frequently caused by defects in mitochondrial fatty acids -oxidation, however defects in lipin metabolism represent the second most common cause of rhabdomyolysis with early onset. This disease is autosomal recessive and is associated with LPIN1 mutations. This genetic study was implemented in our Unit and allowed the identification of the first Portuguese patient with a novel mutation in LPIN1 gene, which contributes to clarify the cause of the disease in this family, to expand the mutational spectrum of this gene and will be important for an accurate genetic counseling. Our data corroborate the importance of the molecular study of the LPIN1 gene to confirm recurrent rhabdomyolysis in children and adults. The molecular characterization of these patients is important as there is a possibility of an adequate treatment.
Rhabdomyolysis results from damage in skeletal muscle fibres and release of intracellular components of the muscle to the bloodstream, which leads to myoglobinuria, and in severe cases, acute renal failure. The most frequent causes of rhabdomyolysis are alcohol and other drugs consumption, excessive physical activity, trauma and infections. As metabolic myopathies are causes of rhabdomyolysis and result from the inability to produce an adequate amount of ATP for muscle needs, due to enzymatic deficiencies in carbohydrates, lipids or nucleosides metabolism. Usually occur in childhood and are expressed by pain, muscle weakness and myoglobinuria after physical exercise, viral infections or fasting, which under normal conditions do not cause muscle necrosis. These diseases are frequently caused by defects in mitochondrial fatty acids -oxidation, however defects in lipin metabolism represent the second most common cause of rhabdomyolysis with early onset. This disease is autosomal recessive and is associated with LPIN1 mutations. This genetic study was implemented in our Unit and allowed the identification of the first Portuguese patient with a novel mutation in LPIN1 gene, which contributes to clarify the cause of the disease in this family, to expand the mutational spectrum of this gene and will be important for an accurate genetic counseling. Our data corroborate the importance of the molecular study of the LPIN1 gene to confirm recurrent rhabdomyolysis in children and adults. The molecular characterization of these patients is important as there is a possibility of an adequate treatment.
Description
Keywords
Rabdomiólise Causas Metabólicas Mutações no gene LPIN1 Doenças Genéticas
Pedagogical Context
Citation
Boletim Epidemiológico Observações. 2016 setembro-dezembro;5(17):41-44
Publisher
Instituto Nacional de Saúde Doutor Ricardo Jorge, IP