Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 3/2022

01-03-2022 | Tremor | Original Article

Postural tremor in L-2-hydroxyglutaric aciduria is associated with cerebellar atrophy

Authors: Aysegul Gunduz, Ayse Cigdem Aktuglu-Zeybek, Damla Tezer, Ece Oge Enver, Tanyel Zubarioglu, Ertugrul Kiykim, Meral E. Kiziltan

Published in: Neurological Sciences | Issue 3/2022

Login to get access

Abstract

Objective

In this study, we performed analysis of brainstem reflexes and movement disorders using surface polymyogram in L-2-hydroxyglutaric aciduria (L2HGA). We also reviewed all cases in the literature with detailed clinical and radiological description to analyze the anatomical correlates of involuntary movements.

Patients and method

We performed surface electromyography of appropriate muscles, long-loop reflexes, and somatosensory evoked potentials and analyzed the neuroimaging findings in patients with L2HGA and recorded blink reflex (BR), auditory startle response (ASR), and startle response after somatosensory stimuli (SSS) in patients and healthy subjects. We also performed a systematic literature search to identify the association of neuroimaging findings and movements disorders in previous patients with L2HGA.

Results

Thirteen patients were enrolled in the study. Among them, ten had low-amplitude postural tremor with a frequency between 4 and 7 Hz. The tremor was predominant on distal parts of the upper extremities. Postural tremor was accompanied by negative myoclonus in one-third. The BR, ASR, and SSS, all, were hypoactive. There was a close association of postural tremor with cerebellar atrophy in patients who participated in this study and by the analysis of the previously reported patients.

Conclusions

Low-amplitude postural tremor is common in L2HGA. It is related with cerebellar atrophy. Although the neuroimaging shows no overt lesions at the brainstem, there is a functional inhibition at this level.
Literature
1.
Kranendijk M, Struys EA, Salomons GS, Van Der Knaap MS, Jakobs C (2012) Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis 35:571–587PubMedPubMedCentralCrossRef
2.
Barbot C, Fineza I, Diogo L et al (1997) L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients. Brain Dev 19:268–273PubMedCrossRef
3.
Steenweg ME, Jakobs C, Errami A et al (2010) An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study. Hum Mutat 31:380–390PubMedCrossRef
4.
Topçu M, Aydin ÖF, Yalçinkaya C et al (2005) L-2-hydroxyglutaric aciduria: a report of 29 patients. Turk J Pediatr 47:1–7PubMed
5.
Zübarioğlu T, Yalçınkaya C, Oruç Ç et al (2020) Evaluation of clinical, neuroradiologic, and genotypic features of patients with l-2-hydroxyglutaric aciduria. Turk Pediatr Ars 55:290–298
6.
Olgac A, Tekin OL, Ezgü FS, Biberoǧlu G, Tümer L (2019) A 7-year-old boy with hand tremors and a novel mutation for L-2-hydroxyglutaric aciduria. Balk J Med Genet 22:93–96CrossRef
7.
Clerc C, Bataillard M, Richard P, Divry P, Kraehenbuhl J, Rumbach L (2000) An adult form of L-2-hydroxyglutaric aciduria revealed by tremor. Eur Neurol 43:119–120PubMedCrossRef
8.
Periasamy V, Rudwan M, Yadav G, Khan RA (2008) Epilepsy in a young adult caused by L-2-hydroxyglutaric aciduria: A case report. Med Princ Pract 17:258–261PubMedCrossRef
9.
10.
Goffette SM, Duprez TP, Nassogne MCL, Vincent MFA, Jakobs C, Sindic CJ (2006) L-2-Hydroxyglutaric aciduria: Clinical, genetic, and brain MRI characteristics in two adult sisters. Eur J Neurol 13:499–504PubMedCrossRef
11.
Samuraki M, Komai K, Hasegawa Y et al (2008) A successfully treated adult patient with L-2-hydroxyglutaric aciduria. Neurology 70:1051–1052PubMedCrossRef
12.
Sass JO, Romrell JS, Vinson SY et al (2009) Tracing the origin of L-2-hydroxyglutaric aciduria in a family. Int J Neurosci 119:2118–2123PubMedCrossRef
13.
14.
Shah H, Chandarana M, Sheth J, Shah S (2020) A case report of chronic progressive pancerebellar syndrome with leukoencephalopathy:L-2 hydroxyglutaric aciduria. Mov Disord Clin Pract 7:560–563PubMedPubMedCentralCrossRef
15.
van der Knaap MS, Valk J, Barth PG, Smit LME, van Engelen BGM, Donati PT (1995) Leukoencephalopathy with swelling in children and adolescents: MRI patterns and differential diagnosis. Neuroradiology 37:679–686PubMedCrossRef
16.
Weimar C, Schlamann M, Krägeloh-Mann I, Schöls L (2013) L-2 hydroxyglutaric aciduria as a rare cause of leukencephalopathy in adults. Clin Neurol Neurosurg 115:765–766PubMedCrossRef
17.
Faiyaz-Ul-Haque M, Al-Sayed MD, Faqeih E et al (2014) Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds. Ann Saudi Med 34:107–114PubMedPubMedCentralCrossRef
18.
Saidha S, Murphy S, McCarthy P, Mayne PD, Hennessy M (2010) L-2-Hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration. J Neurol 257:146–148PubMedCrossRef
19.
Martin AJ, Morales-Briceño H, Tchan M, Fung VSC (2020) The head retraction reflex in Niemann-Pick type C: a novel diagnostic clue. Mov Disord Clin Pract 7:543–547PubMedPubMedCentralCrossRef
20.
Williams DR, Doyle LMF, Lees AJ, Brown P (2008) The auditory startle response in parkinsonism may reveal the extent but not type of pathology. J Neurol 255:628–632PubMedCrossRef
21.
Fujitake J, Ishikawa Y, Fujii H et al (1999) L-2-hydroxyglutaric aciduria: two Japanese adult cases in one family. J Neurol 246:378–382PubMedCrossRef
22.
Gökçen C, Isikay S, Yilmaz K (2013) L-2 Hydroxyglutaric aciduria presenting with anxiety symptoms. BMJ Case Rep 2013:bcr2013009512
23.
Yamamoto T, Yoshioka S, Tsurusaki Y et al (2016) White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria. Brain Dev 38:142–144PubMedCrossRef
24.
Işikay S (2013) L-2 Hydroxyglutaric aciduria presenting with status epilepticus. BMJ Case Rep 2013:bcr2013010164
25.
Isikay S, Carman KB (2013) Contribution of brain MRI in a patient diagnosed with L-2-hydroxyglutaric aciduria. BMJ Case Rep 2013:bcr2013008917
26.
Divry P, Jakobs C, Vianey-Saban C et al (1993) L-2-Hydroxyglutaric aciduria: two further cases. J Inherit Metab Dis 16:505–507PubMedCrossRef
27.
Jović NJ, Kosać A, Koprivšek K (2014) L-2-hydroxyglutaric aciduria: a case report. Srp Arh Celok Lek 142:337–341PubMedCrossRef
28.
Lee C, Born M, Salomons GS, Jakobs C, Woelfle J (2006) Hemiconvulsion-hemiplegia-epilepsy syndrome as a presenting feature of L-2-hydroxyglutaric aciduria. J Child Neurol 21:538–540PubMedCrossRef
29.
Seijo-Martinez M, Navarro C, Castro Del Rio M et al (2005) L-2-hydroxyglutaric aciduria: Clinical, neuroimaging, and neuropathological findings. Arch Neurol 62:666–670PubMedCrossRef
30.
Sztriha L, Gururaj A, Vreken P, Nork M, Lestringant GG (2002) L-2-hydroxyglutaric aciduria in two siblings. Pediatr Neurol 27:141–144PubMedCrossRef
31.
Yilmaz K (2009) Riboflavin treatment in a case with l-2-hydroxyglutaric aciduria. Eur J Paediatr Neurol 13:57–60PubMedCrossRef
32.
Zafeiriou DI, Sewell A, Savvopoulou-Augoustidou P, Gombakis N, Katzos G (2001) L-2-Hydroxyglutaric aciduria presenting as status epilepticus. Brain Dev 23:255–257PubMedCrossRef
33.
Zafeiriou DI, Ververi A, Salomons GS et al (2008) L-2-Hydroxyglutaric aciduria presenting with severe autistic features. Brain Dev 30:305–307PubMedCrossRef
34.
Kamate M, Prashanth GP, Hattiholi V (2014) L-2-hydroxyglutaric aciduria: report of two Indian families. Indian J Pediatr 81:296–298PubMedCrossRef
35.
Karatas H, Saygi S, Bastan B et al (2010) L-2-hydroxyglutaric aciduria: report of four Turkish adult patients. Neurologist 16:44–46PubMedCrossRef
36.
Marcel C, Mallaret M, Lagha-Boukbiza O, Kremer S, Echaniz-Laguna A, Tranchant C (2012) L-2-hydroxyglutaric aciduria diagnosed in a young adult with progressive cerebellar ataxia and facial dyskinesia. Rev Neurol 168:187–191PubMedCrossRef
37.
Mazzei R, Ungaro C, Garreffa G et al (2011) Clinical, genetic and magnetic resonance findings in an Italian patient affected by l-2-hydroxyglutaric aciduria. Neurol Sci 32:95–99PubMedCrossRef
38.
Mete A, Isikay S, Sirikci A, Ozkur A, Bayram M (2012) Eyelid myoclonia with absence seizures in a child with L-2 hydroxyglutaric aciduria: findings of magnetic resonance imaging. Pediatr Neurol 46:195–197PubMedCrossRef
39.
Buijink AWG, Van Der Stouwe AMM, Broersma M et al (2015) Motor network disruption in essential tremor: a functional and effective connectivity study. Brain 138:2934–2947PubMedCrossRef
40.
Fang W, Lv F, Luo T et al (2013) Abnormal regional homogeneity in patients with essential tremor revealed by resting-state functional MRI. PLoS 8:e69199CrossRef
41.
Canda E, Köse M, Yazıcı H et al (2018) Clinical, neuroimaging, and genetic features of the patients with L-2-hydroxyglutaric aciduria. J Pediatr Res 5:39–43CrossRef
42.
Esteban A (1999) A neurophysiological approach to brainstem reflexes. Blink reflex Neurophysiol Clin 29:7–38PubMedCrossRef
43.
Hori A, Yasuhara A, Naito H, Yasuhara M (1986) Blink reflex elicited by auditory stimulation in the rabbit. J Neurol Sci 76:49–59PubMedCrossRef
44.
45.
Kofler M, Müller J, Seppi K, Wenning GK (2003) Exaggerated auditory startle responses in multiple system atrophy: a comparative study of parkinson and cerebellar subtypes. Clin Neurophysiol 114:541–547PubMedCrossRef
46.
Kofler M, Müller J, Wenning GK et al (2001) The auditory startle reaction in parkinsonian disorders. Mov Disord 16:62–71PubMedCrossRef
47.
Kurul S, Çakmakçi H, Dirik E (2004) Glutaric aciduria type 1: proton magnetic resonance spectroscopy findings. Pediatr Neurol 31:228–231PubMedCrossRef
48.
Jequier Gygax M, Roulet-Perez E, Meagher-Villemure K et al (2009) Sudden unexpected death in an infant with L-2-hydroxyglutaric aciduria. Eur J Pediatr 168:957–962PubMedCrossRef
Metadata
Title
Postural tremor in L-2-hydroxyglutaric aciduria is associated with cerebellar atrophy
Authors
Aysegul Gunduz
Ayse Cigdem Aktuglu-Zeybek
Damla Tezer
Ece Oge Enver
Tanyel Zubarioglu
Ertugrul Kiykim
Meral E. Kiziltan
Publication date
01-03-2022
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 3/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-021-05555-x

Other articles of this Issue 3/2022

Neurological Sciences 3/2022 Go to the issue

Original Article

Effects of repetitive transcranial magnetic stimulation on cerebral glucose metabolism

Neuro-Images

Ulnar neuropathy from accessory epitrochlearis anconeus muscle

COVID-19

Masked face recognition in patients with relapsing–remitting multiple sclerosis during the ongoing COVID-19 pandemic

Brief Communication

Arterial intracranial thrombosis as the first manifestation of vaccine-induced immune thrombotic thrombocytopenia (VITT): a case report

Original Article

The cognitive impact of guard shifts in physicians: a before-after study

Original Article

Job satisfaction among physicians and nurses involved in the management of multiple sclerosis: the role of happiness and meaning at work