Dados do Trabalho

Título

SERINE DEFICIENCY: A RARE BUT POTENTIALLY TREATABLE DIAGNOSIS THAT SHOULD NOT BE FORGOTTEN.

Apresentação do caso único

Case presentation: A 4-year-old boy began follow-up in our service with a history of microcephaly, pyramidal syndrome, and regression of neuropsychomotor development starting at 3 months, coinciding with the onset of infantile spasms. Additionally, the patient had congenital cataracts and exhibited dysmorphic features. Intrauterine growth restriction was noted leading to a cesarean delivery at 37 weeks without complications. Relevant family history indicated that the patient's grandmothers were twin sisters and the parents were cousins. On physical examination, the patient showed no eye contact or fixation, and exhibited tetraparesis with axial hypotonia and appendicular hypertonia, along with joint contractures and heightened reflexes. Investigation with MRI revealing unspecific features. Cerebrospinal fluid (CSF), lactate, acylcarnitine profile, amino acid chromatography, and isoelectric focusing of transferrin were normal. Five years later, through the Rare Genomes Project, a condition associated with homozygous mutation in the PHGDH gene was identified, confirming the diagnosis of serine deficiency.

Discussão

Discussion: 3-phosphoglycerate dehydrogenase (PHGDH) deficiency is an inborn error of metabolism accounting for approximately 70% of cases of L-serine deficiency. It is an autosomal recessive condition with unknown prevalence, estimated to have slightly more than fifty reported cases. Individuals typically present with microcephaly at birth or develop it within the first three weeks of life, followed by developmental delay and growth restriction, along with epilepsy before the first year of life. The spectrum of presentations ranges from the lethal prenatal form known as Neu-Laxova syndrome to infantile – as seen in this patient – juvenile, and adult forms. Diagnosis currently relies on molecular genetic testing showing biallelic pathogenic (or likely pathogenic) variants in the PHGDH, PSAT1, or PSPH genes. Additionally, low levels of serine in CSF (usually <13 umol/L) and serum when measured under fasting conditions are noted.

Comentários finais

Final Comments: Despite being a rare disease, its recognition is crucial due to the potential for treatment with serine supplementation. Early initiation of treatment can prevent further developmental delays and neurological damage. Even in patients already affected, administration has shown improvement in seizure control. A dose of 600 mg/kg/day is recommended.

Referências

van der Crabben, Saskia N, and Tom J de Koning. “Serine Deficiency Disorders.” GeneReviews®, edited by Margaret P Adam et. al., University of Washington, Seattle, 22 June 2023.

de Koning TJ, Klomp LW. Serine-deficiency syndromes. Curr Opin Neurol. 2004;17:197-204.

Neurologia Infantil: funtamentos e prática clínica/ [editores] Marcelo Masruha, Luiz Celso Vilanova – São Paulo, SP: Editora dos editores Eireli, 2023. ISBN 978-85-85162-51-1. Capitulo 45, pag 927, volume 2.

Palavras Chave

inborn error of metabolism; Developmental and epileptic encephalopathy; microcephaly