In other species: dog , domestic cat , indicine cattle (zebu) , sheep , Japanese quail

Categories: Lysosomal storage disease

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 232300 (trait) , 606800 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2000

Cross-species summary: Also called Pompe disease, Pompe's disease, acid maltase deficiency, and generalised glycogenesis type II. A lysosomal storage disease in which there is a buildup (storage) of glycogen, due to the lack of the enzyme alpha-glucosidase, whose task is to break down glycogen into its constituent glucose molecules. Characterised by poor growth, incoordination, muscle weakness and eventual recumbency.

Mapping: 19q15

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Dennis et al. (2000) identified two causal mutations in Brahman cattle, namely a frameshifting 2-bp deletion (c.1057delTA; the "E7" mutation) and a nonsense mutation (c.1783C>T; p.Arg595Ter; the "E13" mutation) in the bovine GAA gene; and a 2-bp frameshifting deletion (c.2454delCA; the "E18" mutation) in Shorthorns.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Lyons et al. (2017) reported the presence of the E7 variant in Droughtmaster cattle (a composite breed with some Brahman contribution) at a frequency of 3.4% in their sample of 859 cattle genotyped. These authors stressed that their sample may not be representative of the breed as a whole. Neither the E13 nor E18 variants was detected. By genotyping "930 Braford, 94 Brangus, and 8 Brahman" from Argentina, Caffaro et al. (2019) reported "that 12.02% (95% CI 12.00-12.04) of the total number of samples received were heterozygous (i.e., carriers) for the E7 mutation, while 12.58% (95% CI 12.56-12.60) of the Braford, 6.38% (95% CI 6.26-6.51) of the Brangus, and 12.50% (95% CI 9.82-15.18) of the Brahman samples were carriers of this loss-of-function allele. Neither breed nor sex were significantly associated to the presence of the mutation. The prevalence informed in this study is similar to the average prevalence reported for Australian Brahmans."

Genetic testing: Dennis et al. (2000) developed allele-specific amplification and double mismatch amplification procedures for genotyping the exon 18 alleles in the acidic alpha-glucosidase gene (Mohammad Shariflou 13/11/2006).

Breeds: Brahman (Cattle) (VBO_0000159), Droughtmaster (Cattle) (VBO_0000196), Shorthorn (Cattle) (VBO_0000375).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: