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Neonatal-onset propionic acidemia: neurologic and developmental profiles, and implications for management
K N North1, M S Korson, Y R Gopal
1Department of Medicine, Children's Hospital, Boston, Massachusetts, USA.
Insights
Current therapy improves survival and nutrition in neonatal-onset propionic acidemia (PA). However, hypotonia and cognitive delays persist, necessitating further treatment advances for better outcomes in PA patients.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Propionic acidemia (PA) is an inherited metabolic disorder.
- Neonatal-onset PA presents significant clinical challenges.
Purpose of the Study:
- To document clinical and neurodevelopmental profiles of neonatal-onset PA patients.
- To evaluate the efficacy of current therapies for PA.
Main Methods:
- Prospective evaluation of six PA patients over 15 months.
- Review of historical clinical and biochemical data.
- Assessment of nutritional status, hyperammonemia episodes, and developmental performance.
Main Results:
- Improved survival and nutritional status observed with therapeutic interventions.
- Hypotonia impacted motor development; focal deficits and seizures were absent.
- Mild to moderate intellectual impairment was present in all patients, irrespective of metabolic control.
Conclusions:
- Current PA therapy enhances survival and nutrition, reducing focal neurological deficits.
- Hypotonia and cognitive delays remain challenges even with optimal metabolic control.
- Further therapeutic advancements are crucial for improving developmental and cognitive outcomes in PA.
Objectives:
To document the clinical and neurodevelopmental profiles of a cohort of patients with neonatal-onset propionic acidemia and to determine the efficacy of current therapy with respect to outcome.
Method:
The clinical, neurologic, and developmental status of six patients was prospectively evaluated during a 15-month period. Previous clinical and biochemical data were ascertained from hospital records to determine longitudinal nutritional status, number of episodes of hyperammonemia with ketoacidosis, and developmental performance with respect to age.
Results:
No deaths resulted from propionic acidemia since the identification of the oldest patient in the series in 1980. Therapeutic intervention (e.g., gastrostomy tube feeding) resulted in improved nutritional status and possibly contributed to improved survival. All children had hypotonia, resulting in a significant effect on motor development; however, focal neurologic deficits and evidence of movement or seizure disorder were absent. Mild cortical atrophy was evident on cranial magnetic resonance imaging in four patients. All children, including two patients with no significant episodes of hyperammonemia and normal growth since the neonatal period, had a mild to moderate degree of intellectual impairment.
Conclusions:
The results of our study suggest that current therapy for neonatal-onset propionic acidemia is associated with improved survival and nutritional status, and an absence of focal neurologic deficits. However, hypotonia and cognitive delay were still present, even in children with "optimal" metabolic control. Additional therapeutic advances are required to improve the developmental and cognitive outcome.