Table 2.

Inborn Errors of Metabolism Associated with 3-Methylglutaconic Aciduria

3-MGCAGeneMOIDisorderKey Clinical Characteristics in Addition to 3-MGCA 1
Discriminating feature 2 AGK ARSengers syndrome
(See Mitochondrial DNA Maintenance Defects Overview.)		Cataracts; cardiomyopathy (DD)
AUH ARAUH defect
(OMIM 250950)
  • Nonspecific speech & language delay w/o metabolic derangement in some individuals & w/hypoglycemia & metabolic acidosis in others
  • Failure to thrive, ID, & DD common
  • Microcephaly & progressive neurologic impairment w/spastic quadriplegia, seizures, & dystonia reported 3
CLPB AR CLPB deficiency Cataracts; central hypopnea; DD & ID; movement disorder; neutropenia (epilepsy)
DNAJC19 ARDNAJC19 defect (DCMA syndrome)
(OMIM 610198)
  • Cardiomyopathy; DD & ID; growth restriction; cerebellar ataxia; may be assoc w/optic atrophy
  • Seen in Dariusleut Hutterite population of Canada. 4
HTRA2 ARMGCA8
(OMIM 617248)		Cataracts; central hypopnea; DD & ID; epilepsy; movement disorder; neutropenia
OPA3 AR Costeff syndrome DD; movement disorders; optic atrophy
SERAC1 ARSERAC1 defect
(MEGDEL syndrome)		DD & ID; deafness; movement disorder (epilepsy & optic atrophy)
TAFAZZIN (TAZ)XLTAFAZZIN defect
(Barth syndrome)		Cardiomyopathy; 5 skeletal myopathy; DD; growth restriction; neutropenia
TIMM50 ARMGCA9
(OMIM 617698)		DD & ID; epilepsy
TMEM70 ARTMEM70 defectCardiomyopathy; DD & ID
Occasional feature POLG POLG disorders Encephalopathy w/intractable epilepsy & hepatic failure; DD or dementia, lactic acidosis, & myopathy
SUCLA2 AR SUCLA2 mtDNA depletion syndrome, encephalomyopathic form w/methylmalonic aciduria Hypotonia; epilepsy; muscular atrophy; movement disorder; growth retardation
SUCLG1 AR SUCLG1 mtDNA depletion syndrome, encephalomyopathic form w/methylmalonic aciduria Hypotonia; uncontrolled movement; hearing loss; DD

3-MGCA = 3-methylglutaconic aciduria; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

1.

Features shown in ( )s are rare.

2.

Adapted from Kovacs-Nagy et al [2018], Table 1

3.
4.
5.

Dilated cardiomyopathy presents within the first year of life or even prenatally [Barth et al 2004].

From: Costeff Syndrome

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