Format

Send to

Choose Destination
J Chin Med Assoc. 2017 Apr;80(4):253-261. doi: 10.1016/j.jcma.2016.07.006. Epub 2017 Mar 13.

Experiences during newborn screening for glutaric aciduria type 1: Diagnosis, treatment, genotype, phenotype, and outcomes.

Author information

1
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
2
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
3
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department of Ophthalmology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
4
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
5
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC.
6
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
7
Physical Medicine and Rehabilitation Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
8
Department of Food and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
9
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: dmniu@vghtpe.gov.tw.

Abstract

BACKGROUND:

Glutaric aciduria type 1 (GA-1) is an organic acidemia with potentially severe neurological sequelae. In Taiwan, newborn screening (NBS) for GA-1 began in 2001, but large-scale reporting is lacking. This study describes Taiwan's largest newborn screening population to date.

METHODS:

Between 2001 and 2015, 1,490,636 newborns were screened for GA-1. Confirmatory examinations included the carnitine loading test. Confirmed patients were treated with a low lysine diet, carnitine, and high-energy intake during illness. Clinical, laboratory, and neuroimaging data were analyzed.

RESULTS:

Fourteen newborns were diagnosed with GA-1 (incidence: 1/106,474). C5DC concentration was clearly increased after carnitine loading in the affected newborns, but not in false-positive newborns (p = 0.004), indicating that this test is useful as an adjuvant diagnostic method. Eleven patients followed in our hospital were enrolled, namely nine NBS patients and two patients diagnosed clinically. IVS10-2A>C was the most common mutation. Two novel mutations (T36fs and N291K) were identified. Pendular nystagmus was found in two pediatric GA-1 patients. The corresponding pathology was optic atrophy in one patient, but remained undetermined in the other patient. The frequency of encephalopathic crisis decreased substantially following NBS. Among patients diagnosed by NBS, cognitive functioning was better among patients with good compliance than patients with poor compliance (p = 0.03). Abnormalities were detected by brain MRI including diffusion-weighted imaging and apparent diffusion coefficient maps; these affected various brain regions at different stages of the disease. Basal ganglion injuries occurred after an encephalopathic crisis. White matter disease was prevalent among older patients, either with or without an encephalopathic crisis.

CONCLUSION:

Early diagnosis by newborn screening followed by full compliance with treatment guidelines is important to a good outcome.

KEYWORDS:

Taiwan; glutaric aciduria type 1; newborn screening; nystagmus; optic atrophy

PMID:
28302372
DOI:
10.1016/j.jcma.2016.07.006
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center