Case report of two brothers with infantile Parkinsonism-dystonia (OMIM #613135)

Case presentation: V.H.P.S, male, 7 years old, son of consanguineous parents, born at term, without complications. According to a family report, the patient had reduced movement, abnormal postures in the first year of life, and started follow-up with speech therapy and physical therapy. He had infantile spasms at the age of 1 year and has been using anti-seizure drugs since then. Patient evolved with severe dystonia, protein-calorie malnutrition. Previous exams – 2016 skull MRI without changes. Extended screening for normal EIM. Unchanged eye bottom. Audiometry without alterations. Patient admitted to our service referred for genetics in November 2021. Molecular analysis by complete exome sequencing identified a heterozygous mutation in the SLC6A3 gene - position chr5:1,404,016–1,411,358. Deletion of exons 9 to 11 ENST00000270349. J.M.P.S, male 2 years old, brother of the aforementioned patient, born at term, prenatal and delivery without complications. Family report of sibling-like symptoms with reduced movement since birth, evolving with dystonic postures. Patient started seizures at 2 years of age. Currently using anti-crisis drugs with good control. Patient with severe dystonia and protein-calorie malnutrition.

Discussion: Infantile Parkinsonism is caused by homozygous or compound heterozygous mutations in the SLC6A3 gene. The gene is responsible for encoding a dopamine transporter (DAT1) on chromosome 5p15. The pathophysiology described so far justifies that the loss of presynaptic dopamine transporter function leads to defective dopamine reuptake and progressive accumulation of this neurotransmitter in the synapse, leading to its catabolism. Poor dopamine reuptake leads to depletion of presynaptic stores. Excess extraneuronal dopamine can lead to reduced dopamine production and lead to downregulation of dopaminergic receptors mimicking the symptoms of dopamine deficiency. Affected individuals present with hyperkinesia with orolingual and limb dyskinesia, dystonia and chorea, or hypokinesia with parkinsonian features such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, signs of pyramidal release, and abnormal eye movements. Often these patients are initially diagnosed as having cerebral palsy.

Final comments: Life expectancy is short, most cases described died in adolescence. To date, no disease-modifying treatment has been described.

 

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Publikationsverlauf

Artikel online veröffentlicht:
18. September 2023