Dados do Trabalho

Título

Effects of long-term treatment in a patient with Isovaleric Acidemia

RESUMO

Case Presentation:
An 11-year-old female patient, daughter of consanguineous parents, was born with no complications during pregnancy, childbirth or puerperium. At the age of 3 years, she required hospital admission with a history of recurrent vomiting, fever, metabolic acidosis, lethargy, and diarrhea. It was also reported neuropsychomotor development delay. The patient was suspected to have encephalitis, which led to treatment with ceftriaxone, aciclovir and vancomycin, but remained a concern for underlying metabolic disorder. During hospitalization, the patient presented one convulsive seizure, beginning phenobarbital therapy.
Plasma amino acids and urine for organic acids were performed to investigate metabolic disorders. The metabolic studies revealed a marked excretion of isovalerylglycine, along with a moderate excretion of 3-hydroxy-isovaleric acid. The diagnosis of Isovaleric Acidemia (IVA) was made in the same year. The genetic examination revealed, in homozygous, the variant p.Arg414Trp C>T in the IVD gene (OMIM 607036).
The patient was placed on a protein-restricted diet and use of L-carnitine 100 mg/kg/day therapy. Eight years later, she made significant progress on speech and motor development, with improvement on strength, gait, and academic performance.
Discussion:
IVA is a rare inborn error of leucine metabolism caused by biallelic pathogenic variant in the isovaleryl CoA dehydrogenase (IVD) gene. The accumulation of isovaleric acid, toxic to the central nervous system, is related to the phenotypic abnormalities in this disorder.
Patients may present an acute neonatal form of the disease, leading to massive metabolic acidosis and rapid death in the neonatal period, or a chronic intermittent form, with retarded psychomotor development, aversion to dietary protein, hyperammonemia, and pernicious vomiting. If a patient is not treated on time, the patient may proceed to severe acidosis, coma, and death. Therapy consisting of L-carnitine supplementation and protein restriction may be sufficient for effective management of IVA, starting as soon as possible after birth.
Final Comments:
Our results demonstrate the neurocognitive improvement of long-term treatment with L-carnitine supplementation and protein restriction in our patient with IVA. We encourage the analysis for this disorder when investigating patients with recurrent vomiting and lethargy, born from consanguineous marriage.

Palavras Chave

Isovaleric acidemia. Organic acidurias. Inborn Error of Metabolism. Treatment Outcome.

Área

Neurogenética