TREX-1 related Aicardi-Goutières syndrome improved by Janus kinase inhibitor.
Am J Med Genet A
; 194(5): e63510, 2024 05.
Article
em En
| MEDLINE
| ID: mdl-38135344
ABSTRACT
Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy classically characterized by early onset of severe neurologic injury with basal ganglia calcifications, white matter abnormalities, and progressive cerebral atrophy, along with lymphocytosis and raised interferon alpha (INFα) in the cerebrospinal fluid (CSF). Here, we report a 31/2 year-old patient born with prenatal onset AGS, first manifesting as intra-uterine growth retardation. Cranial ultrasonography and cerebral MRI revealed ventriculomegaly and periventricular and basal ganglia calcifications, along with cerebral atrophy. Perinatal infections and known metabolic disorders were excluded. Both CSF lymphocytosis and raised INFα were present. Molecular analysis disclosed two already described compound heterozygous pathogenic variants in TREX1 (c. 309dup, p.(Thr104Hisfs*53) and c. 506G > A, p.(Arg169His)). The evolution was marked by severe global developmental delay with progressive microcephaly. Promptly, the patient developed irritability, quadri-paretic dyskinetic movements, and subsequently tonic seizures. Sensorineural hearing loss was detected as well as glaucoma. Initially, he was symptomatically treated with trihexyphenidyl followed by levetiracetam and topiramate. At age 22 months, baricitinib (0.4 mg/kg/day) was introduced, leading to normal serum INFα levels. Clinically, dyskinetic movements significantly decreased as well as irritability and sleep disturbance. We confirmed that baricitinib was a useful treatment with no major side effect.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Purinas
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Pirazóis
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Sulfonamidas
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Azetidinas
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Doenças dos Gânglios da Base
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Calcinose
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Doenças Autoimunes do Sistema Nervoso
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Inibidores de Janus Quinases
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Linfocitose
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Malformações do Sistema Nervoso
Limite:
Female
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Humans
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Infant
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Male
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Pregnancy
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article