OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: nicein/kalinin (heterotrimeric protein)

Epidermolysis bullosa
EBL
Epiligrin
Herlitz-Pearson type EB

Blistered skin
Skin lysis

Epidermolysis Bullosa Letalis

Clinical Characteristics

General description (for patients):

EBL is one of several serious skin disorders with severe blistering of the skin.  The infantile form identified in the Holmes County Amish may have its onset before birth with blisters forming in utero and therefore lesions are often present at birth.  Most are on the limbs and trunk with relative sparing of the hands and feet.  They rarely heal and instead the raw tissue beneath constantly seeps serum protein and electrolytes much like thermal burns do and there may significant loss of bodily fluids.  The slightest touch may lead to sloughing of the superficial skin.  Infection is a constant threat and these complications often lead to death within weeks to months.

Medical description: 

Epidermolysis bullosa of all types is a severe form of skin disease but especially so in the infantile or letalis type found in the Amish.  Intrauterine or birth trauma leads to large patches of blisters and bullae that slough at the slightest touch.  Most lesions are on the trunk, some on the limbs but few on the hands and feet.  Despite the most intensive skin care with antibiotics, corticosteroids and high dietary protein, most succumb in weeks or several months due to severe fluid loss and dermal sepsis.  Healing of the denuded areas is hardly ever seen and no scarring takes place.  Those who survive for more than several months develop peculiar perioral or perinasal crusted lesions.

Genetics:

The letalis form found in Holmes County and elsewhere is autosomal recessive.  The defect seems to be in nicein/kalinin, a heterotrimeric glycoprotein present in abnormal form in these patients.  However, no specific mutation seems to be responsible for the majority of cases, likely due to the considerable heterogeneity.  Mutations in at least three genes have been linked to this form of EB.

Treatment:

There is no effective treatment beyond comfort and supportive care.  Few survive beyond 6 months.

Prognosis: 

Life expectancy less than 6 months.

Ancillary treatments and support:

Skin care, antibiotics, delicate physical manipulation.

Specialists and specialty centers: 

Dermatologists, nutritionists, pediatricians.

References:

Cross, H.E., Well, R.S., and Esterly, J.R.:  Inheritance in epidermolysis bullosa letalis.  J. Med. Genet. 5: 189-196, 1968.  PubMed ID: 5751205

Pearson, R.W., Potter, B., and Strauss, F.:  Epidermolysis bullosa hereditaria letalis.  Clinical and histological manifestations and course of the disease.  Arch. Derm. 109: 349-355, 1974.  PubMed ID: 4814936

Schachner, L., Lazarus, G.S., and Dembitzer, H.:  Epidermolysis bullosa hereditaria letalis.  Pathology, natural history, and therapy.  Brit. J. Derm. 96: 51-58, 1977.  PubMed ID: 843437

Resources:

Epidermolysis Bullosa Research Foundation
DebRA
EB Nurse