SERAC1 Deficiency- A New Phenotype

Title:SERAC1 Deficiency- A New Phenotype

Volume: 24 Issue: 16

Author(s): Emanuel Martins*, João Durães, Célia Nogueira, João Gomes, Laura Vilarinho and Carmo Macário

Affiliation:

• Centro Hospitalar e Universitário de Coimbra (Portugal)

Abstract: Introduction: SERAC1 deficiency phenotype range from MEGD(H)EL syndrome, the most severe, to juvenile complicated spastic paraplegia, to adult-onset dystonic features (in only one patient). The MEGD(H)EL syndrome is characterized by (3-methylglutaconic aciduria with deaf-ness-dystonia, [hepatopathy], encephalopathy, and Leigh-like syndrome). Biochemical abnormali-ties: elevated urinary 3 – metilglutaconic and 3-metilglutaric acids, high lactate and alanine in se-rum. Diagnosis is confirmed when biallelic pathogenic variants in SERAC1 gene are found. Brain MRI: basal ganglia lesions and generalized atrophy.

Results/Case Report: A 30-year-old patient with a moderate intellectual disability, developed, since the age of 25, a progressive loss of previous capacities (hand dexterity, oral language), and later subacute generalized dystonic features. Currently he has spastic tetraparesis, dystonia, scoliosis and autistic behavior, with bilateral basal ganglia lesions on brain MRI. Genetic study revealed biallelic pathogenic variants in SERAC1 gene, confirm MEGD(H)EL. A 73 years old patient with cognitive impairment and progressive spastic tetraparesis had multiple periventricular T2 hyperintense le-sions. She has a homozygotic SERAC1 variant NM_032861: exon4:c.T139A: p.F471 (rs112780453), considered benign. Biochemical study revealed elevated plasmatic alanine and uri-nary3-metilglutaconic and 3-metilglutaric acid. This profile is concordant with mitochondrial dys-function and SERAC1 Deficit.

Conclusion: The first patient has the clinical symptoms associated to the MEGD(H)EL syndrome, and the biochemical and genetic confirmation of the diagnosis, without reservations. However, in the second patient, the progressive paraparesis and cognitive impairment did not appear to be caused by multiple sclerosis nor subcortical vascular leukoencephalopathy (without vascular risk factors). The abnormal biochemical profile is suggestive of SERAC1 Deficiency, even without genetic con-firmation. In what should we believe?

Cite this article as:

Martins Emanuel*, Durães João, Nogueira Célia, Gomes João, Vilarinho Laura and Macário Carmo, SERAC1 Deficiency- A New Phenotype, Endocrine, Metabolic & Immune Disorders - Drug Targets 2024; 24 (16) . https://dx.doi.org/10.2174/1871530323666230914114456