A milder form of molybdenum cofactor deficiency type A presenting as Leigh's syndrome-like phenotype highlighting the secondary mitochondrial dysfunction: a case report

Montaha Almudhry; Asuri N Prasad; C Anthony Rupar; Keng Yeow Tay; Suzanne Ratko; Mary E Jenkins; Chitra Prasad

doi:10.3389/fneur.2023.1214137

A milder form of molybdenum cofactor deficiency type A presenting as Leigh's syndrome-like phenotype highlighting the secondary mitochondrial dysfunction: a case report

Front Neurol. 2023 Sep 15:14:1214137. doi: 10.3389/fneur.2023.1214137. eCollection 2023.

Authors

Montaha Almudhry^{1

2}, Asuri N Prasad^{1

3

4}, C Anthony Rupar^{1

3

5}, Keng Yeow Tay^{1

6}, Suzanne Ratko¹, Mary E Jenkins^{1

4}, Chitra Prasad^{1

3}

Affiliations

¹ London Health Sciences Centre, London, ON, Canada.
² Department of Neuroscience, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
³ Department of Pediatrics, Western University, London, ON, Canada.
⁴ Department of Clinical Neurological Sciences, Western University, London, ON, Canada.
⁵ Department of Biochemistry, Western University, London, ON, Canada.
⁶ Department of Medical Imaging, Western University, London, ON, Canada.

Abstract

Background: Molybdenum cofactor deficiency (MoCD) (OMIM# 252150) is an autosomal-recessive disorder caused by mutations in four genes involved in the molybdenum cofactor (MOCO) biosynthesis pathway.

Objectives: We report a milder phenotype in a patient with MOCS1 gene mutation who presented with a Leigh-like presentation.

Case report: We present the case of a 10-year-old boy who was symptomatic at the age of 5 months with sudden onset of dyskinesia, nystagmus, and extrapyramidal signs following a febrile illness. Initial biochemical, radiological, and histopathological findings a Leigh syndrome-like phenotype; however, whole-exome sequencing detected compound heterozygous mutations in MOCS1 gene, c.1133 G>C and c.217C>T, confirming an underlying MoCD. This was biochemically supported by low uric acid level of 80 (110-282 mmol/L) and low cystine level of 0 (3-49), and a urine S-sulfocysteine at 116 (0-15) mmol/mol creatinine. The patient was administered methionine- and cystine-free formulas. The patient has remained stable, with residual intellectual, speech, and motor sequelae.

Conclusion: This presentation expands the phenotypic variability of late-onset MoCD A and highlights the role of secondary mitochondrial dysfunction in its pathogenesis.

Keywords: Leigh-like phenotype; MOCS1; dystonia; molybdenum cofactor deficiency; stroke.

Publication types

Case Reports