Paula and Bobby
Parents of Lillie
Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH
What is Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH?
Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH is a rare disease. It is also known as AOA1 (with hypoalbuminaemia) AOA2 (without hypoalbumihaemia) Ataxia - oculomotor apraxia Ataxia-oculomotor Apraxia 1; Aoa1 Ataxia-oculomotor Apraxia Syndrome; Aoa Ataxia-telangiectasia-like Syndrome Cerebellar Ataxia, Early-onset, With Hypoalbuminemia; Eoca-ha.
Note that minor neurological problems can occur in Cogan's ocular motor apraxia but this entry refers to a group of patients reviewed by Aicardi et al., (1988) with much more serious involvement. The onset is between 2-6 years with a gait ataxia, but then spreading to involve the trunk and upper limbs. This is followed by abnormal eye and head movements, as in ocular motor apraxia, but the difficulty is in the vertical as well as in horizontal axes. In half, there are mild intellectual changes. There are also extrapyramidal abnormalities including chorea and dystonia. Areflexia, and late peripheral neuropathy occurs. After the initial rapid deterioration the condition seems to remain static for many years. A further 22 patients were reported by Barbot et al., (2001). All had in addition a peripheral neuropathy (areflexia, weakness and wasting). All had in addition a peripheral neuropathy (areflexia, weakness and wasting). Note the very late-onset case (40 years) reported by Criscuolo et al., 2005). CPK and AFP might be raised. Some patients with a mutation do not have the oculomotor apraxia (Criscuolo et al., 2006).
Note the clinical similarities with ataxia-telangiectasia . There is no abnormal chromosome breakage and radiation of lymphocytes gives results in the intermediate range and clearly different from ataxia telangiectasia (Gascon et al., 1995). There is clear evidence of recessive inheritance there being both sibs and consanguinity. Note however the mother and daughter pair reported by Bassuk et al., (2007). Both had the same senataxin mutations (N603D and Q653K in cis). These act synergistically giving a dominant negative effect. The ataxia/tremor was mild and a peripheral neuropathy was not found..
Nemeth et al., (2000) mapped the gene to 9q34 in a large consanguineous Pakistani family. do Ceu Moreira et al., (2001) studied 13 Portuguese families and found linkage to 9p13 in two large and three smaller families with haplotype sharing. Three other families were excluded from this locus. Linkage to 9p13 was also suggested in two families with early onset cerebellar ataxia and hypoalbuminemia, so far only described in Japan. Hypoalbuminaemia was also found in the five Portuguese families mapped to 9p13 by do Ceu Moreira et al., (2001).
Date et al., (2001) and do Ceu Moreira et al., (2001) reported mutations in a ubiquitously expressed gene that they called aprataxin. This protein showed distant homology with polynucleotide kinase 3'-phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins.
Mutations were found both in families with and without immune deficiency. The condition is said to be the commonest form of autosomal recessive ataxia in Japan and the second most common after Friedreich's ataxia in Portugal.
Further cases were reported by Le Ber et al., (2003). Fourteen patients were identified from 9 families and 5 mutations were found. Cerebellar ataxia (with atrophy on MRI) and a severe axonal neuropathy were found in all, oculomotor apraxia in 86%, hypoalbuminaemia in 83% and hypercholesterolaemia in 75%. Cognitive impairment was found in all of those tested. These authors suggest that the five Japanese children, two of whom were sibs, reported by Tachi et al., (2000), have same condition. Three sibs were reported by Mahajinah et al., (2005) who had a mutation in APTX. A mild cognitive defect was found in 2.
Further mutations in senataxin were reported by Duquette et al., (2005) in Quebec. Interestingly, these are the same Quebec families that were reported by Bouchard and Bouchard (1980). They had a distal amyotrophy, a motor-sensory neuropathy and tremor.
* This information is courtesy of the L M D.
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What gene changes cause Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH?
The syndrome is inherited in the following inheritance pattern/s:
Autosomal Recessive - Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation that occurs during the reproductive process.
OMIM Number - 208920 (please check the OMIM page for updated information)
The syndrome can be caused by mutations in the following gene/s location/s:
APTX - 9p21.1
MRE11 - 11q21
What are the main symptoms of Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH?
The typical symptoms of the syndrome are:
Gaze-evoked nystagmus, Gait ataxia, Cognitive impairment, Incoordination, Hyporeflexia, Hypercholesterolemia, Hypoalbuminemia, Hypometric saccades, Truncal ataxia, Limb ataxia, Muscle weakness, Mental deterioration, Medial flaring of the eyebrow, Tremor, Autosomal recessive inheritance, Pes cavus, Adult onset, Juvenile onset, Scoliosis, Ataxia, Choreoathetosis, Cerebellar atrophy, Areflexia, Peripheral axonal degeneration, Oculomotor apraxia, Decreased number of large peripheral myelinated nerve fibers, Progressive external ophthalmoplegia, Distal sensory impairment, Distal amyotrophy, Dystonia, Dysarthria
How does someone get tested for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH?
The initial testing for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia; EAOH can begin with facial genetic analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the type of genetic testing needed. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
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