3-Methylglutaconic Aciduria, Type Iv

Description

The category of 3-methylglutaconic aciduria type IV (MGCA4) represents a heterogeneous unclassified group of patients who share mild or intermittent urinary excretion of 3-methylglutaconic acid. MGCA excretion is a nonspecific finding observed in many other disorders caused by defects in mitochondrial energy metabolism (Gunay-Aygun, 2005).

For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (250950)

Clinical Features

Chitayat et al. (1992) described an 18-year-old man, born of consanguineous Italian parents, with severe psychomotor retardation. At birth, he showed poor growth, was hypotonic, with absent reflexes and respiratory distress. Congenital deformities included bilateral inguinal hernia, undescended testes, subaortic stenosis with biventricular hypertrophy, and right simian crease with left bridged simian crease. He later developed seizures, spasticity, and sensorineural hearing loss. Brain MRI showed cerebellar hypoplasia. Laboratory studies showed mild 3-methylglutaconic and 3-methylglutaric aciduria. The features were inconsistent with other known forms of MGCA, and the authors chose to designate this patient as having '3-methylglutaconic aciduria type IV.' Chitayat et al. (1992) noted that the MGCA excretion was likely a marker for an as yet unidentified primary metabolic disorder.

Wortmann and Morava (2011) stated that dysmorphic features are commonly present in patients with MGCA4. Most of the dysmorphism appears during the course of the disease, secondary to basal ganglia involvement (mask-like facies), muscle wasting of the facial musculature, and hypotonia, leading to an elongation of the face and long, prominent ears. Wortmann and Morava (2011) noted that some of the facial features, such as broad and tall forehead and curved eyebrows, are comparable to those described in Barth syndrome (302060).