Not otherwise specified 3-MGA-uria type

Alternate names

3 alpha methylglutaconic aciduria type IV; 3 methylglutaconic aciduria type IV

Definition

3-methylglutaconic aciduria (3-MGA) type IV, or unclassified 3-MGA, is a clinically heterogeneous disorder characterised by increased 3-methylglutaconic acid excretion in individuals that cannot be classified as having one of the other forms of 3-MGA (3-MGA I, II or III).

Epidemiology

The prevalence of this disorder is unknown.

Cause

The cause remains unknown, unlike patients with 3-MGA type I, individuals with 3MGA type IV display normal 3-methylglutaconyl-CoA hydratase activity in cultured fibroblasts. Mitochondrial respiratory chain abnormalities have been detected in some 3MGA type IV patients but the clinical heterogeneity associated with this disorder suggests that the 3-methylglutaconic aciduria seen in 3-MGA type IV patients may result from a variety of causes and genetic factors.

Inheritance

Autosomal recessive inheritance, a 25% chance

The disorder has been reported to be inherited as an autosomal recessive trait.

Signs and symptoms

• Patients usually present during the first year of life with neurological findings including psychomotor retardation, hypotonia, developmental delay, seizures and progressive spasticity, together with severe failure to thrive.
• Cardiomyopathy, hepatic dysfunction, eye anomalies, microcephaly, deafness, dysmorphism, neonatal hypoglycaemia, thrombocytopaenia and lactic acidosis have also been reported.
• Cerebellar dysgenesis may be revealed by magnetic resonance imaging. In contrast, a small number of asymptomatic patients have been diagnosed as having 3-MGA type IV.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• 3-Methylglutaconic aciduria
• Failure to thrive(Faltering weight)
• Global developmental delay
• Intellectual disability(Mental deficiency)
• Muscular hypotonia(Low or weak muscle tone)
• Seizure
• Spasticity(Involuntary muscle stiffness, contraction, or spasm)

30%-79% of people have these symptoms

• Dysgenesis of the cerebellar vermis

5%-29% of people have these symptoms

• Cardiomyopathy(Disease of the heart muscle)
• Cataract(Clouding of the lens of the eye)
• Decreased liver function(Liver dysfunction)
• Hearing impairment(Deafness)
• Hypoglycemia(Low blood sugar)
• Iris [[hypopigmentation](Light eye color)
• Lactic acidosis(Increased lactate in body)
• Microcephaly(Abnormally small skull)
• Thrombocytopenia(Low platelet count)

Diagnosis

3-methylglutaconic aciduria can be diagnosed by analysis of urinary organic acid excretion but specific diagnosis of 3-MGA type IV requires exclusion of all other forms of 3-MGA. As the genetic factors responsible for the other forms of 3-MGA have now been determined, molecular analysis provides a valuable tool for accurate diagnosis.

Treatment

At present there is no effective treatment for 3-MGA type IV and a leucine-restricted diet appears to be of no benefit.

Prognosis

The prognosis depends on the clinical phenotype but the neurological complications can be severe with a potentially fatal disease course.

NIH genetic and rare disease info

• NIH info on Not otherwise specified 3-MGA-uria type

Not otherwise specified 3-MGA-uria type is a rare disease.

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