Optic nerve atrophy in propionic acidemia

doi:10.1016/S0161-6420(03)00573-6

Ophthalmology

Volume 110, Issue 9, September 2003, Pages 1850-1854

https://doi.org/10.1016/S0161-6420(03)00573-6 Get rights and content

Abstract

Objective

Propionic acidemia is a rare metabolic disorder that is diagnosed in the early neonatal period. The disorder is characterized by life-threatening ketoacidosis, lethargy, failure to thrive, and developmental delay. Herein we report the ocular findings in a prospective series of six patients with propionic acidemia.

Design

Prospective case series.

Participants

Six children (three male and three female) between the ages of 2 and 10 years with propionic acidemia who were examined at Children's Hospital Los Angeles.

Methods

A complete ophthalmic examination was performed on each of the six children. The examination included visual acuity testing, ocular motility, anterior segment examination, and funduscopic evaluation. Emphasis was placed on the function of the optic nerve and on the appearance of the optic disc, looking for possible atrophic changes.

Main outcome measures

The clinical appearance of the optic disc and evidence of optic neuropathy.

Results

Optic nerve atrophy was present exclusively in all of the male patients in the series; none of the female patients demonstrated any detectable impairment of optic nerve function. The optic nerve atrophy was symmetric and age dependent and varied from moderate to severe. There were no other anterior or posterior segment abnormalities, other than one case of unilateral morning glory syndrome, diagnosed at birth. There was no correlation between metabolic control and the development and progression of optic nerve atrophy.

Conclusions

Males with propionic acidemia have moderate to severe bilateral optic atrophy.

Section snippets

Materials and methods

All patients at Children’s Hospital Los Angeles with a diagnosis of propionic acidemia were evaluated by an ophthalmologist at the hospital eye clinic between September and December 2001. Six patients from five unrelated families were identified and recruited for the study: three girls and three boys, including one boy and one girl who were siblings. All had been diagnosed with propionic acidemia at birth and were being closely monitored by both the genetics clinic and the nutrition clinic at

Results

The results of ophthalmologic evaluations for each of the six patients are outlined in Table 1.

None of the three female patients reviewed (ages 4, 6, and 7 years, respectively) had ophthalmic abnormalities on examination, and each one demonstrated normal visual function and ocular anatomic features. The 4-year-old girl had good bilateral fixation and follow, appropriate for her age, with no anterior or posterior segment abnormalities and a normal optic disc. The 6- and 7-year-old girls had

Discussion

This observational study identifies a novel association between propionic acidemia and optic nerve atrophy. In our series of six consecutive patients, all three males manifested some degree of optic nerve atrophy with no known underlying cause. Our results indicate that only two factors seem to be associated with the development of optic nerve atrophy in propionic acidemia—male gender and age.

Progressive and symmetrical optic nerve atrophy is a manifestation of several known metabolic, toxic or

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Propionic acidemia (PA) is an organic acidemia which has a broad range of neurological complications, including developmental delay, intellectual disability, structural abnormalities, metabolic stroke-like episodes, seizures, optic neuropathy, and cranial nerve abnormalities. As the PA consensus conference hosted by Children's National Medical Center progressed from January 28 to 30, 2011, it became evident that neurological complications were common and a major component of morbidity, but the role of imaging and the basis for brain pathophysiology were unclear. This paper reviews the hypothesized pathophysiology, presentation and uses the best available evidence to suggest programs for treatment, imaging, and monitoring the neurological complications of PA.
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Propionic acidemia is a relatively rare inborn error of metabolism. Individuals with propionic acidemia often have life-threatening episodes of hyperammonemia and metabolic acidosis, as well as intellectual disability. There are many reports of additional problems, including poor growth, stroke-like episodes of the basal ganglia, seizures, cardiomyopathy, long QTc syndrome, immune defects, pancreatitis and optic neuropathy; however, there is little information about the incidence of these problems in this rare disease. Additionally, there are no clear guidelines for medical or surgical management of individuals with propionic acidemia. Through a comprehensive and systematic review of the current medical literature and survey of expert opinion, we have developed practice guidelines for the chronic management of individuals with propionic acidemia, including dietary therapy, use of medications, laboratory monitoring, chronic health supervision, use of gastrostomy tubes and liver transplantation.
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Propionic acidemia is an organic acidemia that can lead to metabolic acidosis, coma and death, if not treated appropriately in the acute setting. Recent advancements in treatment have allowed patients with propionic acidemia to live beyond the neonatal period and acute presentation. The natural history of the disease is just beginning to be elucidated as individuals reach older ages. Recent studies have identified the genomic mutations in the genes PCCA and PCCB. However, as of yet no clear genotype–phenotype correlations are known. As patients age, the natural progression of propionic acidemia illuminates intellectual difficulties, increased risk for neurological complications, including stroke-like episodes, cardiac complications, and gastrointestinal difficulties, as well as a number of other complications. This article reviews the available literature for the natural history of propionic acidemia.

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Manuscript no. 220510.

None of the authors has any financial interest relating to this article.

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Original articleOptic nerve atrophy in propionic acidemia☆

Abstract

Objective

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Section snippets

Materials and methods

Results

Discussion

J Pediatr

Brain Dev

J Pediatr

Brain Dev

J Pediatr

Brain Res Dev Brain Res

Toxicol Lett

Exp Neurol

Am J Ophthalmol

Lancet

Prenatal diagnosis of propionic acidemia

JAMA

Original article
Optic nerve atrophy in propionic acidemia☆