HUT (Hutterite)

Inheritance: autosomal recessive
Genes: DNAJC19

3-methylglutaconic aciduria type V
MGA Type V
MGA5
DCMA

Cerebellar ataxia
Dilated cardiomyopathy
Growth failure
Motor delay
Anemia
Mental reatrdation
Testicular dysgenesis
Cryptorchidism
Hypospadias
Long QT interval
Optic atrophy

Cardiomyopathy, Dilated, With Ataxia

Clinical Characteristics

General description (for patients): 

This is a form of heart disease associated with unsteadiness and other neurological disease including mental retardation in some cases.  The heart disease, consisting of enlargement and irregular beating, is present before the age of three years.  Males often have genital anomalies.

Medical description:  

This is a metabolic disorder with severe cardiac and neurological consequences.  Dilated cardiomyopathy is usually evident before the age of three years and is associated with growth and mental retardation. Long QT intervals and arrhythmias occur.  (Long QT intervals also are a feature of the Jervell and Lange-Neilsen syndrome).  Cerebellar ataxia and motor delays are also features.  Testicular dysgenesis with cryptorchidism and severe hypospadias are present in most males.  Heart failure and sudden cardiac death occurs in 70%. In spite of the often serious heart disease, the dllated cardiomyopathy may improve and the EKG may return to normal even after cardiac treatment is discontinued.  Elevated levels of 3-methylglutaconic acid and 3-methylglutaric acid are found in both plasma and urine.  Liver enzymes may also be elevated.

Genetics:  

A mutation in the DNAJC19 gene encoding a purported mitochondrial membrane protein is responsible for the cardiac and neurological phenotype.  The gene is located on chromosome 3 (3q26.3).  It is an autosomal recessive mitochondrial transport disorder and has been reported in 18 Canadian Hutterite patients who were homozygous for a splice-site mutation (IVS3-1 G>C) in the DNAJC19 gene.  A 568 C>T mutation in LMNA has been reported among the Amish of Eastern Pennsylvania.

Treatment:  

No treatment is known beyond that for heart failure.

Prognosis:  

Most patients die from cardiac failure at a young age.

Ancillary treatments and support:  

Treatment for cardiac failure.

Specialists and specialty centers: 

Cardiologist, internist/pediatrician, neurologist.

References:

Davey, K.M., Parboosingh, J.S., McLeod, D.R., Chan, A., Casey, R., Ferreira, P., Snyder, F.F., Bridge, P.J., and Bernier, F.P.: Mutation of DNAJC19, a human homologue of yeast inner mitochondrial co-chaparones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.  J. Med. Genet. 43: 385-393, 2006.  PubMed ID: 16055927

Resources:

The Cardiomyopathy Association
Little Hearts