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3-Hydroxyisobutyric aciduria

MedGen UID:
90996
Concept ID:
C0342737
Disease or Syndrome
Synonym: Disorder of valine metabolism
SNOMED CT: 3-Hydroxyisobutyric aciduria (237957007)
 
Monarch Initiative: MONDO:0009371
OMIM®: 236795
Orphanet: ORPHA939

Definition

A rare classic organic aciduria characterized by tissue accumulation and elevation of urinary excretion of 3-hydroxyisobutyric acid. The clinical phenotype ranges from recurrent mild episodes of vomiting with normal cognitive development, to massive acidosis, seizures, and failure to thrive with profound intellectual disability and early death. Dysmorphic craniofacial features (such as microcephaly, triangular face, short, sloping forehead, long, prominent philtrum, and micrognathia) and variable cerebral anomalies have also been described. [from ORDO]

Clinical features

From HPO
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Abnormality of neuronal migration
MedGen UID:
324748
Concept ID:
C1837249
Congenital Abnormality
An abnormality resulting from an anomaly of neuronal migration, i.e., of the process by which neurons travel from their origin to their final position in the brain.
Congenital intracerebral calcification
MedGen UID:
870518
Concept ID:
C4024966
Congenital Abnormality
The presence of calcium deposition within brain structures that is present already at the time of birth.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Ketoacidosis
MedGen UID:
67434
Concept ID:
C0220982
Disease or Syndrome
Acidosis resulting from accumulation of ketone bodies.
Episodic ketoacidosis
MedGen UID:
349256
Concept ID:
C1859860
Finding
Intermittent episodes of ketoacidosis.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV3-Hydroxyisobutyric aciduria
Follow this link to review classifications for 3-Hydroxyisobutyric aciduria in Orphanet.

Recent clinical studies

Etiology

Sass JO, Walter M, Shield JP, Atherton AM, Garg U, Scott D, Woods CG, Smith LD
J Inherit Metab Dis 2012 May;35(3):437-42. Epub 2011 Aug 24 doi: 10.1007/s10545-011-9381-x. PMID: 21863277
Sasaki M, Yamada N, Fukumizu M, Sugai K
Brain Dev 2006 Oct;28(9):600-3. Epub 2006 May 19 doi: 10.1016/j.braindev.2006.03.007. PMID: 16713161
Chitayat D, Meagher-Villemure K, Mamer OA, O'Gorman A, Hoar DI, Silver K, Scriver CR
J Pediatr 1992 Jul;121(1):86-9. doi: 10.1016/s0022-3476(05)82549-1. PMID: 1625099

Diagnosis

Meyer M, Hollenbeck JC, Reunert J, Seelhöfer A, Rust S, Fobker M, Biskup S, Och U, Linden M, Sass JO, Marquardt T
J Inherit Metab Dis 2021 Nov;44(6):1323-1329. Epub 2021 Jul 5 doi: 10.1002/jimd.12410. PMID: 34176136
Crippa BL, Leon E, Calhoun A, Lowichik A, Pasquali M, Longo N
Am J Med Genet A 2015 Mar;167A(3):621-8. doi: 10.1002/ajmg.a.36939. PMID: 25691415
Sass JO, Walter M, Shield JP, Atherton AM, Garg U, Scott D, Woods CG, Smith LD
J Inherit Metab Dis 2012 May;35(3):437-42. Epub 2011 Aug 24 doi: 10.1007/s10545-011-9381-x. PMID: 21863277
Sasaki M, Iwata H, Sugai K, Fukumizu M, Kimura M, Yamaguchi S
Brain Dev 2001 Jul;23(4):243-5. doi: 10.1016/s0387-7604(01)00196-6. PMID: 11377004
Podebrad F, Heil M, Beck T, Mosandl A, Sewell AC, Böhles H
Clin Chim Acta 2000 Feb 25;292(1-2):93-105. doi: 10.1016/s0009-8981(99)00210-7. PMID: 10686279

Prognosis

Boulat O, Benador N, Girardin E, Bachmann C
J Inherit Metab Dis 1995;18(2):204-6. doi: 10.1007/BF00711767. PMID: 7564247

Clinical prediction guides

Meyer M, Hollenbeck JC, Reunert J, Seelhöfer A, Rust S, Fobker M, Biskup S, Och U, Linden M, Sass JO, Marquardt T
J Inherit Metab Dis 2021 Nov;44(6):1323-1329. Epub 2021 Jul 5 doi: 10.1002/jimd.12410. PMID: 34176136
Podebrad F, Heil M, Beck T, Mosandl A, Sewell AC, Böhles H
Clin Chim Acta 2000 Feb 25;292(1-2):93-105. doi: 10.1016/s0009-8981(99)00210-7. PMID: 10686279

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