Hereditary spastic paraplegia type 35 in a Turkish girl with fatty acid hydroxylase-associated neurodegeneration
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Ayşenur Engin Erdal
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Burak Yürek
Abstract
Objectives
The fatty acid 2-hydroxylase gene (FA2H) compound heterozygous or homozygous variants that cause spastic paraplegia type 35 (SPG35) (OMIM # 612319) are autosomal recessive HSPs. FA2H gene variants in humans have been shown to be associated with not only SPG35 but also leukodystrophy and neurodegeneration with brain iron accumulation.
Case presentation
A patient with a spastic gait since age seven was admitted to the paediatric metabolism department. She was born to consanguineous, healthy Turkish parents and had no family history of neurological disease. She had normal developmental milestones and was able to walk at 11 months. At age seven, she developed a progressive gait disorder with increased muscle tone in her lower limbs, bilateral ankle clonus and dysdiadochokinesis. She had frequent falls and deteriorating school performance. Despite physiotherapy, her spastic paraplegia was progressive. Whole exome sequencing (WES) identified a homozygous NM_024306.5:c.460C>T missense variant in the FA2H gene, of which her parents were heterozygous carriers. A brain MRI showed a slight reduction in the cerebellar volume with no iron deposits.
Conclusions
Pathogenic variants of the FA2H gene have been linked to neurodegeneration with iron accumulation in the brain, leukodystrophy and SPG35. When patients developed progressive gait deterioration since early childhood even if not exhibited hypointensity in the basal ganglia detected by neuroimaging, FA2H-related neurodegeneration with brain iron accumulation should be ruled out. FA2H/SPG35 disease is characterised by notable clinical and imaging variability, as well as phenotypic diversity.
Acknowledgments
We would like to thank the families of our patients.
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Research ethics: The case study was designated exempt from evaluation by the regional institutional review board.
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Informed consent: In this case report, verbal informed consent was obtained from our patient’s family.
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Author contributions: Each author has agreed to be responsible for the complete manuscript’s content and has given approval for submission.
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Competing interests: There are no declared conflicts of interest by the authors.
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Research funding: None declared.
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Data availability: Not applicable.
References
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© 2024 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
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- Editorial
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- Case Reports
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- Hereditary spastic paraplegia type 35 in a Turkish girl with fatty acid hydroxylase-associated neurodegeneration
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Artikel in diesem Heft
- Frontmatter
- Editorial
- Insulin for “hearts that had lost hope” – on the first pediatric patients and the 1923 Nobel Prize in Physiology or Medicine
- Reviews
- The effect of gonadotropin-releasing hormone analog treatment on the endocrine system in central precocious puberty patients: a meta-analysis
- Artificial intelligence in paediatric endocrinology: conflict or cooperation
- Original Articles
- A pilot study proposing an algorithm for pubertal induction in cerebral palsy
- Thyroid volume in Turkish school-age children living in an iodine-sufficient region
- Hypothyroxinemia and weight velocity in preterm infants
- Factors associated with neonatal hyperinsulinemic hypoglycemia, a case-control study
- Predictive factors for lung metastasis in pediatric differentiated thyroid cancer: a clinical prediction study
- Case Reports
- Two Turkish patients with Primary Coenzyme Q10 Deficiency-7: case report and literature review
- Hereditary spastic paraplegia type 35 in a Turkish girl with fatty acid hydroxylase-associated neurodegeneration
- A case report of odonto-hypophosphatasia with a novel variant in the ALPL gene
- Neuronal ceroid lipofuscinosis type 11 diagnosed patient with bi-allelic variants in GRN gene: case report and review of literature
- Diagnosis and approach of pseudohypoparathyroidism type 1A and related disorders during long term follow-up: a case report
