Glutaric Acidemia Type 2
Description
Clinical Characteristics
Without treatment, patients with the neonatal variety will die during an acute attack. Patients with the late-onset form will experience exercise intolerance.
Symptoms are usually triggered by illness (high fever, vomiting, dehydration); crises may also be triggered by vaccinations and surgery. Children may be healthy until the first metabolic crisis. Profuse sweating may occur in some affected children. Acute decompensation has not been reported after 6 years of age, although some undiagnosed patients have presented with a leukoencephalopathy after this age. [Kölker: 2006]
- Facial dysmorphism - high forehead, depressed nasal bridge, low-set abnormally formed ears
- Rocker bottom feet
- Renal anomalies
- Anomalies of the external genitalia
- Virtually all patients with congenital anomalies will die within a week of birth.
- Hypotonia
- Tachypnea
- Metabolic acidosis
- Hepatomegaly
- Sweaty feet odor
- Lab findings:
- Metabolic acidosis
- Hypoglycemia
- Exercise-induced muscle pain
- Movement disorder
Primary Care Management
Next Steps After a Positive 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 Aciduria Type 2 (C4 & C5) (ACMG) (
347 KB)
Confirming the Diagnosis
- To confirm the diagnosis, work with Newborn Screening Services (see RI providers [2]).
- Follow-up testing includes 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.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Medical Genetics (see RI providers [4]).
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill. See Glutaric Acidemia Type 2 - Information for Parents (STAR-G) for additional information. for additional information).
- Support implementation and maintenance of low fat, low protein diet.
- Glucose, intralipids, carnitine, and fluids given intravenously may be indicated during episodes of acute, intercurrent illness.
- 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.
Resources
Information & Support
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.
For Professionals
Glutaric Acidemia Type 2 (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
For Parents and Patients
Support
Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.
General
Glutaric Acidemia Type 2 - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Glutaric Acidemia Type 2 (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
Tools
ACT Sheet for Glutaric Aciduria Type 2 (C4 & C5) (ACMG) ( 347 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Confirmatory Algorithms for Glutaric Acidemia Type 2 (ACMG) ( 190 KB)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American
College of Medical Genetics.
Services for Patients & Families in Rhode Island (RI)
Service Categories | # of providers* in: | RI | NW | Other states (4) (show) | | MT | NM | NV | UT |
---|---|---|---|---|---|---|---|---|---|
Medical Genetics | 4 | 1 | 8 | 4 | 5 | 6 | |||
Newborn Screening Services | 2 | 1 | 4 | 1 | 2 | 3 |
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
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.
Kölker S, Garbade SF, Greenberg CR, Leonard JV, Saudubray JM, Ribes A, Kalkanoglu HS, Lund AM, Merinero B, Wajner M, Troncoso
M, Williams M, Walter JH, Campistol J, Martí-Herrero M, Caswill M, Burlina AB, Lagler F, Maier EM, Schwahn B, Tokatli A, Dursun
A, Coskun T, Chalmers RA, Koeller DM, Zschocke J, Christensen E, Burgard P, Hoffmann GF.
Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency.
Pediatr Res.
2006;59(6):840-7.
PubMed abstract
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