A rare metabolic disorder, glutaryl acidemia type 1 (GA1), is characterized by a deficiency of the enzyme glutaryl-CoA dehydrogenase.
Causes
In GA1, the glutaryl-CoA dehydrogenase enzyme is made by mutations in the GCDH gene. Consequently, the enzyme's activity is reduced or absent, resulting in accumulation of toxic substances and harmful levels of glutaric acid in the body.
Symptoms
GA1 typically manifests during infancy or early childhood. Common symptoms include:
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The accumulation of cerebrospinal fluid causes macrocephaly, enlargement of the head.
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Floppy movements are caused by hypotonia, a decrease in muscle tone.
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Sitting, crawling, and walking milestones are delayed in children with developmental delays.
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As a result of involuntary muscle contractions, dystonia leads to abnormal postures and movements.
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A seizure is an abnormal electrical activity in the brain, which may vary in severity and frequency.
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An acute encephalopathic crisis is a sudden worsening of symptoms triggered by illness, fever, or other stressors, which can lead to coma or death if left untreated.
Diagnosis
Clinical evaluation, biochemical testing, and genetic testing are used to diagnose GA1. Diagnostic steps may include:
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Blood or urine samples are tested for glutaric acid and its metabolites in newborns.
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A quantitative analysis of glutaryl-CoA dehydrogenase activity in blood or skin cells confirms the diagnosis.
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Testing for GCDH mutations using DNA analysis to confirm the diagnosis and assess the risk of the condition in other family members.
Treatment
GA1 is mainly treated by preventing metabolic crises and managing symptoms. Treatment options include:
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A low-protein diet can help minimize the accumulation of toxic metabolites by reducing the intake of glutaric acid precursors, such as lysine and tryptophan.
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The supplementation of carnitine can improve the excretion of toxic metabolites and optimize energy metabolism.
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Implementing emergency protocols to manage acute metabolic crises, including intravenous fluids, glucose administration, and seizure medications.
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By improving muscle tone, strength, and motor skills, physical therapy can minimize the risk of musculoskeletal complications.
Prevention
The prevention of complications associated with GA1 involves early detection through newborn screening and proactive management of the condition. Prevention strategies may include:
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Ensure all newborns are screened for GA1 as part of routine newborn screening programs to enable early diagnosis and intervention.
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Monitor glutaric acid and its metabolites regularly to assess metabolic control and detect metabolic decompensation.
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The goal is to educate patients, families, and caregivers about the signs and symptoms of metabolic crises and provide access to resources and medical professionals who are experienced in managing GA1.
Conclusion
There is an accumulation of toxic metabolites in the body as a result of a deficiency of the enzyme glutaryl-CoA dehydrogenase in glucose acidemia type 1. Macrocephaly, hypotonia, developmental delays, dystonia, seizures, and acute encephalopathic crises are typical symptoms during infancy and early childhood. In addition to newborn screening, biochemical testing, and genetic testing are also used to diagnose the condition. Through dietary management, supplementation, emergency protocols, and physical therapy, metabolic crises can be prevented and symptoms managed. Prevention strategies include newborn screening, regular monitoring, education, and support.
