Home > Newborn Disorders > Glutaric acidemia type 2
Glutaric acidemia type 2
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100% [Schulze: 2003]Names
Glutaric acidemia type 2
Glutaric acidemia II (GA2, GA II)
Glutaric aciduria type 2
Multiple acyl-CoA dehydrogenase deficiency (MAD, MADD)
Electron transfer flavoprotein dehydrogenase deficiency (ETFA, ETFB, ETFDH)
Overview
Glutaric acidemia type 2 is caused by a deficiency of one of three electron transfer flavoprotein enzymes (ETFA, ETFB, or ETFDH). Patients are unable to produce energy from fats and proteins resulting in hypoglycemia, weakness, and in severe cases infant death. Three forms of the condition exist - neonatal onset with congenital anomalies, neonatal onset without anomalies, and a late-onset or mild form that may be amenable to treatment. More recently, a form due to defective transport of riboflavin (the cofactor of the ETF complex) has been reported (Brown-Vialetto-Van Laere and Fazio Londe syndrome) [Bosch: 2011]. The differences in clinical presentation relate to the amount of residual enzyme activity.Prevalence
about 1/250,000 live births [Schulze: 2003]Clinical Characteristics
With treatment, possible only in the milder forms, some of the neurologic sequelae and the carnitine deficiency may be avoided. Death within the first few weeks is almost invariable in those with the neonatal or congenital anomaly form. Without treatment, patients with the neonatal variety will die during an acute attack. Patinets with the late-onset form will experience exercise intolerance.Initial signs and symptoms may include: In the neonatal with anomalies form:
- facial dysmorphism - high forehead, depressed nasal bridge, low-set abnormally formed ears
- rocker bottom feet
- muscular defects of the abdominal wall
- renal anomalies
- anomalies of the external genitalia and
- virtually all patients with congenital anomalies will die within a week of birth.
In the neonatal without anomalies form, illness generally presents within the first few days, including:
- hypotonia
- tachypnea
- metabolic acidosis
- hepatomegaly
- sweaty feet odor
- lab findings:
- metabolic acidosis
- hypoglycemia
Those with mild or late-onset form may present with:
- exercise-induced muscle pain
- movement disorder
Treatment consists of fasting avoidance, carnitine and riboflavin supplements.
Follow-up on positive screening test
Quantitative plasma acylcarnitine profile, urine organic acid and acylglycine analysis, confirmation with ETF/ETF-QO enzyme assay and/or gene sequencing. If negative, consider riboflavin transporter deficiency if biochemical abnormalities (plasma acylcarnitine profile) are persistent.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for facial dysmorphism, poor feeding, vomiting, lethargy, odor of sweaty feet;
- Provide emergency treatment/referral for signs or symptoms of hypoketotic hypoglycemia, metabolic acidosis, hyperammonemia,
cardiomyopathy (see ACT Sheet for Glutaric acidemia type 2 (ACMG)
(
347 KB)
for additional information);
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
If the diagnosis is confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Glutaric acidemia type 2 info for parents (STAR-G) for additional information);
- Support implementation and maintenance of low fat, low proteindiet;
- Oral L-carnitine, riboflavin, or glycine supplements may be indicated;
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management.Resources
Information & Support
For Professionals
Glutaric acidemia type 2 info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
Glutaric acidemia type 2, late onset, info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
ACT Sheet for Glutaric acidemia type 2 (ACMG)
( 347 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Resources for Glutaric acidemia type 2 (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Glutaric acidemia type 2 (OMIM)
Extensive review of the literature, including clinical features and genetics, from the Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE,
and links to other scientific information and sites.
Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions
screened for.
For Parents and Patients
Glutaric acidemia type 2 info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about glutaric
acidemia 2 and links to other sites including parent support groups.
Glutaric acidemia type 2 (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Fatty Oxidation Disorders (FOD) Family Support Group
The FODsupport.org site offers a variety of information for families about fatty acid oxidation disorders, support groups,
coping, finances, and links to other sites.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 3/2011 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 4/2011 |
Page Bibliography
Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham
HR.
Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD:
a new inborn error of metabolism with potential treatment.
J Inherit Metab Dis.
2011;34(1):159-64.
PubMed abstract / Full Text
High dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome, as well as for the Fazio Londe syndrome,
which is considered to be the same disease entity without the deafness.
Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome,
and implications.
Pediatrics.
2003;111(6 Pt 1):1399-406.
PubMed abstract