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Episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome) caused by a novel mutation in ADPRHL2 (AHR3)

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Abstract

Background

The protein “ADP-Ribosylarginine Hydrolase-Like Protein 2” is encoded by ADPRHL2 and reverses ADP-ribosylation. Recently, mutations in ADPRHL2 were found to be associated with a very rare childhood onset severe neurodegeneration syndrome with episodic, stress-induced seizures, ataxia, and axonal neuropathy. In this study, we evaluate a novel mutation in ADPRHL2 leading to an unknown adult onset syndrome “episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome).”

Design/methods

Four patients with episodic psychosis, ataxia, and motor neuropathy with pyramidal signs were included in this study.

Results

An index patient presented ataxia, postural tremor in the hands, and hallucinations at age 20 years, which had started after a viral infection. She improved within 3 months without any treatment. Her neurological exam revealed mild distal weakness, brisk DTRs, bilateral Babinski sign, impaired vibration sensation, position, and ataxia. Pes cavus and hammer toes were also noted. EMG revealed neurogenic changes in distal muscles and normal sensory nerve conduction studies. Cranial MRI was normal. She had three more severe episodes in recent years, and her neurologic findings got progressively worse. Two of her older sisters had much milder phenotypes. The phenotype of the fourth patient from an unrelated family was identical with the index patient. All affected patients had homozygous novel NM_017825.3:c.838G>A (p.Ala280Thr) mutations in a highly conserved region of ADPRHL2. Western blot analyses demonstrated that ADPRHL2 was not expressed in these patients.

Conclusions

Here, we describe a novel mutation in ADPRHL2, which further expands the phenotypic and genetic spectrum of the patients harboring these mutations.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Istanbul University, 34390, Capa, Istanbul, Turkey

    Hacer Durmus & Yesim Parman

  2. Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul, Turkey

    Elif Mertoğlu & Evren Önay Uçar

  3. Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    Heinrich Sticht & Said Hashemolhosseini

  4. Intergen Genetic Diagnosis and Research Center, Ankara, Turkey

    Serdar Ceylaner

  5. Department of Psychiatry, Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Işın Baral Kulaksızoğlu

Authors
  1. Hacer Durmus
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  2. Elif Mertoğlu
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  3. Heinrich Sticht
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  4. Serdar Ceylaner
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  5. Işın Baral Kulaksızoğlu
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  6. Said Hashemolhosseini
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  7. Evren Önay Uçar
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  8. Yesim Parman
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Contributions

Dr. Hacer Durmus had evaluated the patients clinically, designed the study, and wrote the manuscript.

Dr. Elif Mertoğlu analyzed and interpreted the genetic and Western blot data.

Dr. Heinrich Sticht analyzed and interpreted the data and made critical revisions of the manuscript for important content.

Dr. Serdar Ceylaner generated, analyzed, and interpreted the genetic data.

Dr. Işın Baral Kulaksızoğlu had evaluated the patients.

Dr. Evren Önay Uçar had analyzed and interpreted the genetic data and contributed to manuscript writing.

Dr. Said Hashemolhosseini analyzed and interpreted the data and made critical revisions of the manuscript for important content.

Dr. Yesim Parman had evaluated the patients, supervised the study, and made critical revisions of the manuscript for important content.

Corresponding author

Correspondence to Hacer Durmus.

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The authors declare no competing interests.

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The written informed consent was obtained from all subjects prior to participating in these study.

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Durmus, H., Mertoğlu, E., Sticht, H. et al. Episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome) caused by a novel mutation in ADPRHL2 (AHR3). Neurol Sci 42, 3871–3878 (2021). https://doi.org/10.1007/s10072-021-05100-w

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  • DOI: https://doi.org/10.1007/s10072-021-05100-w

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