Diagnosis of autism in a rare case of tyrosine hydroxylase deficiency: a case report

Abstract

Background Tyrosine hydroxylase deficiency (THD) is a rare movement disorder with broad phenotypic expression caused by bi-allelic mutations in the TH gene, which encode for tyrosine hydroxylase (TH) protein. Some patients with THD have improvement in dystonia with carbidopa–levodopa, a synthetic form of dopamine typically used in Parkinson’s disease, and are considered to have dopa-responsive THD. THD has been found in 0.5–1 per million persons, although due to overlapping symptoms with other disorders and the need for genetic testing, prevalence is likely underestimated. Existing literature describes some patients with THD having intellectual disability, but comorbid autism spectrum disorder (ASD) has not been reported. Case presentation A nearly 3-year-old boy was referred to pediatric neurology due to hypotonia, delayed motor milestones, and expressive speech delay. Whole exome sequencing confirmed tyrosine hydroxylase deficiency, detecting a novel variant p.S307C first reported here. The child was treated with carbidopa–levodopa with an excellent response, resulting in improved balance, fewer falls, and improved ability to jump, run and climb stairs. He was determined to have dopa-responsive THD. Due to his delays in expressive speech, the boy also had an assessment with a developmental and behavioral pediatrician, who identified a pattern of social pragmatic speech delay, sensory sensitivities, and restricted interests, and determined that he met criteria for a diagnosis of ASD. Conclusions While ASD can stand alone as a clinical diagnosis, it is also a cardinal feature of other genetically-based neurological disorders. To our knowledge, this is the first case that describes a patient with both disorders. Perhaps THD may be among the genetic disorders linked with ASD.

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes

“…We compiled the summary from Dong et al, encompassing all TH deficiency cases reported through 2018 (Dong et al, 2020) and all Segawa patients published thereafter until 2023 (Atanasoska et al, 2023;Bijarnia-Mahay et al, 2020;Champagne et al, 2022;Chen et al, 2020;Couto et al, 2019;Hou et al, 2019;Hull et al, 2021;Janssen et al, 2021;Kuseyri Hubschmann et al, 2021;Panda et al, 2022;Reyes et al, 2023;Wang et al, 2022). In total, we summarized the clinical phenotypes of all 175 reported Segawa cases.…”

“…Until now, more than 100 cases of Segawa syndrome have been reported globally (Reyes et al, 2023). However, due to the rarity and high heterogeneity of Segawa syndrome, the spectrum of pathological mutations in the TH gene, associated clinical symptoms, and the correlation between genotype and phenotype, as well as genotype and treatment outcomes with dopamine, are not fully understood (Chen et al, 2020;Dong et al, 2020;Reyes et al, 2023). Further studies are required to enhance our comprehension of this disease.…”