Objective: Present a case of movement  disorder that genetic panel hasn’t tracked in the screening, and it’s stabilization with L-carnitine.

Background: isobutyryl-CoA dehydrogenase deficiency is rare recessive metabolic disorder, resulting from variants in ACAD8, and is poorly understood. Feng and colbs, have noticed elevated C4-acylcarnitine levels, and fewer Isobutyrylglycine in their 40 patient screening paper. 

Patients with IBDD are either asymptomatic or symptomatic with variable clinical features, including failure to thrive, seizures, anaemia, hypotonia, and development delay.Some symptomatic patients had normal growth and development with carnitina supplementation.

Method: JAB, 15yo, global developmental delay, with motor difficulties in manipulating objects, dropping glasses and taking food to the mouth in tetradystonia, neonatal hearing loss. She’s studying 1st year of high school with regular academic performance with tutoring. Independent for daily activities. He has an anxious profile, with initial insomnia. Performs physiotherapy once a week, echinotherapy, speech therapy. Estimated weight of 42kg. He’s having perioral and cervical botulinum toxin application.Taking artane 5mg 8/8h, L carnitine 20% 5ml 12/12h, fluoxetine 20mg.

Consider tetradystonic, with fine tremors, walking with a wide gait, preserved strength, sensitivity and deep reflexes. 

Features reveals low weight and height, sardonic laughter, cervical dystonia, dystonia in four limbs, mild dysmetria, fine tremors and mild gait ataxia. Furthermore, the clerk’s cramps were noticeable.

Results: Free carnitine 31 and total 44, carnitine esters 13, blood count Hb 13.4, giant platelets. A negative movement panel was carried out, exome and mitochondrial DNA of Jun/22 compatible with isobutyl coa dehydrogenase deficiency (OMIN:611283), heterozygous mutation in the ACAD8 gene. Imaging exams, as a normal cranial MRI. 

The disease stopped progressing clinically during the period of treatment with L-carnitine.

Conclusion: Although the mutation of the ACAD8 gene leading to Isobutyl-CoA dehydrogenase deficiency is well known in the literature, there is no description of movement disorders in these patients. In our case, the patient presents not just one, but four changes (tremor, ataxia, generalized dystonia and task-specific dystonia). The presence of sardonic laughter is also relevant, a classic finding in Wilson’s disease, but which is far from being pathognomonic.

References: Koeberl DD, Young SP, Gregersen NS, Vockley J, Smith WE, Benjamin DK Jr, An Y, Weavil SD, Chaing SH, Bali D, McDonald MT, Kishnani PS, Chen YT, Millington DS. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2003 Aug;54(2):219-23. doi: 10.1203/01.PDR.0000074972.36356.89. Epub 2003 May 7. PMID: 12736383.

Sass JO, Sander S, Zschocke J. Isobutyryl-CoA dehydrogenase deficiency: isobutyrylglycinuria and ACAD8 gene mutations in two infants. J Inherit Metab Dis. 2004;27(6):741-5. doi: 10.1023/B:BOLI.0000045798.12425.1b. PMID: 15505379.

Feng J, Yang C, Zhu L, Zhang Y, Zhao X, Chen C, Chen QX, Shu Q, Jiang P, Tong F. Phenotype, genotype and long-term prognosis of 40 Chinese patients with isobutyryl-CoA dehydrogenase deficiency and a review of variant spectra in ACAD8. Orphanet J Rare Dis. 2021 Sep 20;16(1):392. doi: 10.1186/s13023-021-02018-6. Erratum in: Orphanet J Rare Dis. 2021 Dec 7;16(1):505. PMID: 34544473; PMCID: PMC8454130.

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