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Clinical and laboratory findings and etiologies of genetic homocystinemia: a single-center experience

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Abstract

Background

Homocysteine (Hcy) is an endogenous nonprotein sulfur-containing amino acid biosynthesized from methionine by the removal of its terminal methyl group. Hyperhomocysteinemia (HHcy) has been linked to many systemic disorders, including stroke, proteinuria, epilepsy, psychosis, diabetes, lung disease, and liver disease. The clinical effects of high serum Hcy level, also known as hyperhomocysteinemia, have been explained by different mechanisms. However, little has been reported on the clinical and laboratory findings and etiologies of genetic HHcy in children. This study aimed to examine the relationships between clinical features, laboratory findings, and genetic defects of HHcy.

Methods

We retrospectively evaluated 20 consecutive children and adolescents with inherited HHcy at the pediatric neurology division of Baskent University, Adana Hospital (Adana, Turkey) between December 2011 and December 2022.

Results

Our main finding is that the most common cause of genetic HHcy is MTHFR mutation. The other main finding is that the Hcy level was higher in patients with CBS deficiency and intracellular cbl defects than in MTHFR mutations. We also found that clinical presentations of genetic HHcy vary widely, and the most common clinical finding is seizures. Here, we report the first and only case of a cbl defect with nonepileptic myoclonus. We also observed that mild and intermediate HHcy associated with the MTHFR mutation may be related to migraine, vertigo, tension-type headache, and idiopathic intracranial hypertension. Although some of the patients were followed up in tertiary care centers for a long time, they were not diagnosed with HHcy. Therefore, we suggest evaluating Hcy levels in children with unexplained neurological symptoms.

Conclusions

Our findings suggest that genetic HHcy might be associated with different clinical manifestations and etiologies. Therefore, we suggest evaluating Hcy levels in children with unexplained neurologic symptoms.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

Abbreviations

Hcy:

Homocysteine

HHcy:

Hyperhomocysteinemia

EEG:

Electroencephalographic

MRI:

Magnetic resonance imaging

PPH:

Primary pulmonary hypertension

FSGS:

Focal glomerular sclerosis

CBS:

Cystathionine b-synthase

CSF:

Cerebrospinal fluid pressure

IIH:

İDiopathic cranial hypertension

RAO:

Retinal artery occlusion

MR:

Mental retardation

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Funding

The authors declare that this study did not receive any financial support.

Author information

Authors and Affiliations

  1. Division of Neurology, Faculty of Medicine, Adana Dr. Turgut Noyan Teaching and Medical Research Center, Baskent University, Adana, Turkey

    Seyda Besen & Ilknur Erol

  2. Division of Pediatrics, Faculty of Medicine, Adana Teaching and Medical Research Center, Baskent University, BarajYolu 1 Durak, Seyhan, 01120, Adana, Turkey

    Yasemin Ozkale

  3. Clinical Genetics Unit, Intergen Genetics and Rare Diseases Research and Application Center, Ankara, Turkey

    Serdar Ceylaner

  4. Division of Nephrology, Faculty of Medicine, Adana Dr. Turgut Noyan Teaching and Medical Research Center, Baskent University, Adana, Turkey

    Aytul Noyan

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  1. Seyda Besen
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Contributions

ŞB wrote the manuscript. ŞB, YÖ, İE, SC, and AN were involved in patient care, including administration of medication and routine clinical follow-up. İE, YÖ, ŞB reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Yasemin Ozkale.

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Conflict of interest

The authors declare there are no conflicts of interest financial or otherwise related to the material presented herein.

Ethical approval

Our study was approved by the Baskent University Institutional Review Board and Ethics Committee. The approvement number is KA20/120. Written informed consent was obtained from the parents of all participants.

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The authors disclosed government work.

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Besen, S., Ozkale, Y., Ceylaner, S. et al. Clinical and laboratory findings and etiologies of genetic homocystinemia: a single-center experience. Acta Neurol Belg 124, 213–222 (2024). https://doi.org/10.1007/s13760-023-02356-1

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