Early Diagnosed and Treated Glutaric Acidemia Type 1 Female Presenting with Subependymal Nodules in Adulthood

Abstract

Glutaric acidemia type 1 (GA-1, OMIM no. 231670) is an autosomal recessive disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH). The subsequent accumulation of the amino acids lysine, hydroxylysine, and tryptophan and their breakdown intermediates can be neurotoxic and particularly cause injury to the basal ganglia.

Roughly 1 of 100,000 infants is affected with GA-1, and a common feature at birth is macrocephaly. Stress, such as in febrile illnesses, can precipitate encephalopathic crises in children generally less than 2 years with variable recovery. Many infants develop dystonia with complex movement disorders and subtle cognitive and fine motor deficits. Common neuroradiologic findings include hypoplasia of temporal and frontal lobes, striatal lesions, white matter changes, and subdural effusions.

There are three previous reports of subependymal nodules found on neuroimaging in GA-1 patients who were diagnosed as adults and untreated for GA-1. We present a unique case of an adult female who was diagnosed at age 2 months and managed prior to any metabolic decompensation. Her initial diagnosis was made based on biochemical and enzymatic analysis, and then later confirmed with genetic sequencing. She started experiencing frequent headaches at age 12 years. Neuroimaging in adulthood revealed common features seen in GA-1 in addition to the finding of subependymal nodules.

This case may provide some insight into the natural progression of the disease despite early treatment. Though subependymal nodules are typically seen in tuberous sclerosis, the significance of these lesions in GA-1 is not well understood. Disease courses of more early diagnosed and treated patients with GA-1 need to be documented.

Appendices

Synopsis

We report the first case of subependymal nodules in an adult, without any stigmata for tuberous sclerosis, who was diagnosed and treated for glutaric acidemia type 1 since infancy without any metabolic decompensation.

Compliance with Ethics Guidelines

Conflict of Interest

All authors (Bimal Patel, Surekha Pendyal, Priya Kishnani, Marie McDonald, and Lauren Bailey) declare there are neither competing interests nor financial disclosures.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the patient included in this study.

Animal Studies

This chapter does not contain any studies with animal subjects performed by the any of the authors.

Authorship Contributorship Statements

All authors have been involved in (a) conception and design, or analysis and interpretation of data, and (b) drafting the chapter or revising it critically for important intellectual content.

All coauthors have seen the final version of the chapter, confirm that the work has not been published/submitted elsewhere, and agree with submission.

Bimal Patel::

conception and design, analysis, interpretation of data, writing/drafting of the manuscript, final approval of chapter.

Surekha Pendyal::

conception and design, analysis, interpretation of data, final approval of chapter.

Priya Kishnani::

primary physician caring for patient since early childhood, conception and design, analysis, interpretation of data, final approval of chapter.

Marie McDonald::

conception and design, analysis, interpretation of data, final approval of chapter.

Lauren Bailey::

genetic counselor caring for patient, conception and design, analysis, interpretation of data, final approval of chapter.