FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: infantile cerebellar-retinal degeneration
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General Information
Name
infantile cerebellar-retinal degeneration
FlyBase ID
FBhh0000511
Disease Ontology Term
Parent Disease
OMIM
INFANTILE CEREBELLAR-RETINAL DEGENERATION; ICRD
Overview

This report describes infantile cerebellar-retinal degeneration (ICRD); ICRD is inherited as an autosomal recessive. The human gene implicated in this disease is aconitase 2 (ACO2), an enzyme of the citric acid (TCA) cycle. There are two orthologous Drosophila genes: mAcon1, a high-scoring ortholog that is widely expressed; and mAcon2, a moderate-scoring ortholog that exhibits testis-specific expression. Amorphic mutations have been generated for mAcon1; RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for both Drosophila genes.

The human ACO2 gene has not been introduced into flies.

Animals homozygous for amorphic mutations of Dmel\mAcon1 die during embryogenesis. Partial loss of function effected by RNAi results in decreased viability; surviving adults exhibit reduced locomotor activity, a much shorter lifespan, increased cell death in the developing brain, and appear to have a decreased metabolic rate compared to controls. Reduced triacylglyceride levels and increased acetyl-CoA are observed, suggesting that lipids are used as an energy source via fatty acid oxidation, to compensate for the impaired glycolysis and TCA cycle. Physical and genetic interactions for Dmel\mAcon1 have been reported; see below and in the gene report for mAcon1.

[updated Oct. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: infantile cerebellar-retinal degeneration
OMIM report

[INFANTILE CEREBELLAR-RETINAL DEGENERATION; ICRD](https://omim.org/entry/614559)

Human gene(s) implicated

[ACONITASE 2; ACO2](https://omim.org/entry/100850)

Symptoms and phenotype

Infantile cerebellar-retinal degeneration (ICRD) is a severe neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia (low muscle tone), athetosis (involuntary writhing movements), seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation (Spiegel et al., 2012; pubmed:22405087). [from MIM:614559; 2017.03.03]

(OMIM, 2013-)
Genetics

Infantile cerebellar-retinal degeneration (ICRD) is caused by homozygous or compound heterozygous mutation in the aconitase-2 gene (ACO2); autosomal recessive. [from MIM:614559; 2017.03.03]

(OMIM, 2013-)
Cellular phenotype and pathology

Brain MRI shows progressive cerebral and cerebellar degeneration (Spiegel et al., 2012; pubmed:22405087). [from MIM:614559; 2017.03.03]

(OMIM, 2013-)
Molecular information

Aconitase 2 (ACO2) belongs to the aconitase/IPM isomerase family; it is encoded in the nucleus and functions in the mitochondrion. It catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the citric acid (Krebs, TCA) cycle. [Gene Cards, ACO2; 2017.03.03]

(FlyBase Curators, 2013-)
External links
Disease synonyms
ICRD
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    ACO2; aconitase 2
    D. melanogaster ortholog (based on DIOPT)
    Dmel\mAcon1
    (DIOPT, 2013-)
    Dmel\mAcon2
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to many (1 human to 2 Drosophila).

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\mAcon1
      Gene Snapshot
      Mitochondrial aconitase 1 (mAcon1) encodes a mitochondrial iron-sulfur enzyme that catalyses the second step of the tricarboxylic acid (TCA) cycle, converting citrate into isocitrate via a cis-aconitase intermediate. [Date last reviewed: 2018-09-13]
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human ACO2 (2 Drosophila to 1 human). Dmel\Acon shares 72% identity and 83% similarity with ACO2.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      H. sapiens (Human)
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (40 groups)
        mAcon1
        protein-protein
        Interacting group
        Assay
        References
        mAcon1 - Act79B
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Act88F
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Actn
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Adh
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Aldo
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Argk1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ATPsynB
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ATPsynCF6
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ATPsynD
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ATPsynF
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ATPsynO
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - CG7920
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - COX7AL2
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Cs1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Cyt-c1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Cyt-c-p
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Eno
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - fln
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Gdh
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Gpdh1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Gpo1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - GstS1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Mdh2
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Mf
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Mhc
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Mlc1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Mlc2
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Mpcp1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ND-18
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - ND-PDSW
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Ogdh1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Prm
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Scp1
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - stumps
        two hybrid
        (Battersby et al., 2003)
        mAcon1 - Tm2
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - TpnC4
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - TpnC41C
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - Tppl
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - up
        experimental knowledge based
        (Guruharsha et al., 2011)
        mAcon1 - wupA
        experimental knowledge based
        (Guruharsha et al., 2011)
        Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
        mAcon1
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        mAcon1GD1348
        model of  infantile cerebellar-retinal degeneration
        CEA
        (Cheng et al., 2013)
        Modifiers Based on Experimental Evidence ( 3 )
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Related mammalian, viral, bacterial, or synthetic transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        mAcon1GD1348
        P{GD1348}
        w1118; P{GD1348}v11767
        mAcon1RNAi.UAS
        P{UAS-mAcon1.RNAi}
        w*; P{UAS-mAcon1.RNAi}115
        mAcon1KK100999
        P{KK100999}
        P{KK100999}VIE-260B
        mAcon1HMS00998
        P{TRiP.HMS00998}
        y1 sc* v1 sev21; P{TRiP.HMS00998}attP2
        mAcon1NIG.9244R
        P{NIG.9244R}
        P{NIG.9244R}1
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        mAcon1MB09176
        w1118; Mi{ET1}mAcon1MB09176/SM6a
        mAcon11
        ethyl methanesulfonate
        References (5)