APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal recessive
Genes: ALS2

ALS
Juvenile ALS
ALSJ
ALS2

Muscle weakness

Fasiculations

Hyperreflexia

Spasticity

Slurred speech

Muscle atrophy

APA

Amyotrophic Lateral Sclerosis 2, Juvenile Onset

Clinical Characteristics

General description (for patients):  

This is a progressive neurological disorder with weakness, muscle wasting, and spasticity.  Onset occurs early as walking is delayed and even then is clumsy.  Speech may be slurred later.  Physical labor during youth causes shortness of breath and excessive tiredness.  Walking becomes increasingly difficult due to foot and toe deformities (club foot).  The most important diagnostic feature is spontaneous twitching of muscles in the limbs and in the tongue.

Medical description:  

Juvenile ALS has many of the clinical features of adult-onset ALS except for its apparent autosomal recessive mode of inheritance and earlier onset.  Children begin walking late and even then may be considered ‘clumsy’.  Dysarthria occurs late in the first decade.  Generalized muscle weakness is progressive leading to dyspnea and excessive fatigue with mild exertion even during the first decades.  Muscle atrophy, especially of the interosseous and hypothenar muscles can be marked.  Fasiculations in skeletal and tongue muscles are present but not marked.  Hyperreflexia is present in all limbs and pes cavus can lead to difficulty walking.  Pseudobulbar symptoms are sometimes seen but cerebellar signs are absent.  Many of the clinical features and the general course are not unlike that of the Troyer syndrome except the latter does not exhibit fasiculations.

Genetics:  

ALS2 is probably an autosomal recessive based on the few reported families in which the parents were consanguineous.  Mapping has pinned down a locus on chromosome 2 (2q33) containing a gene (ALS2) encoding alsin.  A Turkish male, born of consanguineous parents, with this presumed disease has been found to have a homozygous deletion (553delA) in this gene.  His normal parents and two brothers were heterozygous.  Two brothers and a distant relative belonging to the Lancaster Amish community have been described as having this disorder.  The parents of the brothers were consanguineous.

Treatment:  

No treatment is known.

Prognosis:  

Weakness and disability are progressive with dyspnea the most disabling.

Ancillary treatments and support:

General supportive care and assistance with locomotion.

Specialists and specialty centers:  

Neurologist.

References:

Gregg, G.W., Fogelson, M.H., and Zwirecki, R.J.:  Juvenile amyotrophic lateral sclerosis in two brothers from an inbred community. In:  Medical Genetic Studies of the Amish. The Johns Hopkins Press, Baltimore, MD.  Pp. 154-158, 1978. PubMed ID: 5173366

Kress, J.A., Kuhnlein, P., Winter, P., Ludolph, A.C., Kassubek, J., Muller, U., and Sperfeld, A.D.:  Novel mutation in the ALS2 gene in juvenile amyotrophic lateral sclerosis.  Ann. Neurol. 58: 800-803, 2005.  PubMed ID: 16240357

Resources:

The ALS Association
ALS Division of the Muscular Dystrophy Assocation