3 hydroxyisobutyric aciduria

Signs and symptoms

3-Hydroxyisobutyric aciduria typically presents during the prenatal period. These patients typically have dysmorphic characteristics such as a small triangular face, low-set ears, a long philtrum, and microcephaly. Individuals may exhibit a wide range of phenotypes, from mild episodes of vomiting accompanied by normal brain and cognitive development to severe mental impairment, delayed motor development, and early death.

Causes

It was previously assumed that 3-hydroxyisobutyrate dehydrogenase (HIBADH) deficiency in the valine catabolic pathway was the underlying enzyme defect, but new evidence suggests that individuals with 3-hydroxyisobutyryic aciduria represent a heterogeneous group that has various underlying mechanisms, such as respiratory chain defects or methylmalonate semialdehyde dehydrogenase deficiency.

Diagnosis

When in stable condition, patients with 3-Hydroxyisobutyric aciduria excrete elevated amounts of 3-Hydroxyisobutyric acid (3-HIBA) in urine, ranging from 60 to 390 mmol/mol of creatinine and increasing to 10,000 mmol/mol creatinine during acute ketoacidosis episodes.

Treatment

There is limited evidence and no agreement on treatment; protein restriction and carnitine supplementation have been used.

References

References

1. (January 8, 2021). "3-hydroxyisobutyric aciduria".
2. (August 24, 2011). "3-Hydroxyisobutyrate aciduria and mutations in the ''ALDH6A1'' gene coding for methylmalonate semialdehyde dehydrogenase". Wiley.
3. (2006). "Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria". Elsevier BV.
4. (1992). "Brain dysgenesis and congenital intracerebral calcification associated with 3-hydroxyisobutyric aciduria". Elsevier BV.