[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Citations 0
Special Feature
July 1998

Picture of the Month

Arch Pediatr Adolesc Med. 1998;152(7):708. doi:
Denouement and Discussion: Cutaneous Lesions Associated With Isoleucine Deficiency

Figure 1 and Figure 2. The rash is erythematous, desquamating, and most prominent in the diaper area where it began. The perioral area is spared in this infant.

Methylmalonic aciduria (MMA) is a disorder of branched-chain amino acid metabolism in which methylmalonic acid accumulates in body fluids. Infants with this disorder usually present in the first few weeks of life with vomiting, acidosis, and ketonuria. Lethargy, hypotonia, and coma may ensue. Associated laboratory abnormalities may include hyperammonemia, neutropenia, and thrombocytopenia. If undiagnosed, recurrent episodes of vomiting, dehydration, and ketoacidosis may lead to mental retardation and death.

Methylmalonic aciduria is the result of a defect in the enzyme methylmalonyl CoA mutase, which requires adenosylcobalamin, a metabolite of vitamin B12, as a coenzyme. Two forms of the mutase apoenzyme deficiency have been described—mut0, referring to no detectable enzyme activity, and mut−, indicating abnormally reduced enzyme activity.1 About half of the patients with MMA have a deficiency of the mutase apoenzyme and are not responsive to vitamin B12 therapy. The other half of patients with a defect in the formation of adenosylcobalamin are responsive to vitamin B12 treatment. Treatment of the mutase-deficient patients includes a diet low in threonine, isoleucine, valine, and methionine.

A rash, in many cases similar to the rash of acrodermatitis enteropathica, has been described in several metabolic disorders, including MMA,2,3 maple syrup urine disease,46 propionic acidemia,3 and citrullinemia.7 The first 3 disorders are closely related inborn errors of branched-chain amino acid metabolism, and they usually require strict restriction of branched-chain amino acids as part of dietary therapy. In the patients with rash and very low serum concentrations of isoleucine, institution of isoleucine supplementation resulted in rapid clearing of the rash.3,5,6

The rash of acrodermatitis enteropathica usually begins in the periorificial areas of the body (anus, mouth, nose, and eyes) as moist, erythematous lesions that may become vesicular or bullous. As the lesions dry, the resulting plaques often resemble psoriatic lesions. The lesions spread to the extremities and may involve the trunk as well. Zinc deficiency is the cause of the rash and the associated findings. In many children the rash described in the infants with branched-chain amino acid disorders is similar to the rash of acrodermatitis enteropathica, although the rash did not have a perioral component in this infant and in some of the children with MMA described in other reports.2 The rash may be more precisely described as an exfoliative erythroderma in many infants with branched-chain amino acid disorders who have developed low isoleucine levels.

Acrodermatitis enteropathicalike rashes have been described in several other disorders including essential fatty acid deficiencies, biotin-responsive multiple carboxylase deficiency, cystic fibrosis, kwashiorkor, and necrolytic migratory erythema.3,6

Accepted for publication August 15, 1997.

Corresponding author: Masayuki Sasaki, MD, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187, Japan.

Fenton  WARosenberg  LE Disorders of propionate and methylmalonate metabolism. Scriver  CRBeaudet  ALSly  WSValle  Deds. The Metabolic Basis of Inherited Disease. New York, NY McGraw-Hill Book Co Inc1995;1423- 1449Google Scholar
Koopman  RJJHapple  R Cutaneous manifestations of methylmalonic acidemia.  Arch Dermatol Res. 1990;282272- 273Google ScholarCrossref
De Raeve  LDe Meirleir  LRamet  JVandenplas  YGerlo  E Acrodermatitis enteropathica-like cutaneous lesions in organic aciduria.  J Pediatr. 1994;124416- 420Google ScholarCrossref
Spraker  MKHelminski  MAElsas  LJ Peri-orificial dermatitis secondary to deficiency of isoleucine in treated infants with maple syrup urine disease [abstract].  J Invest Dermatol. 1986;4508Google Scholar
Northrup  HSigman  ESHebert  AA Exfoliative erythroderma resulting from inadequate intake of branched-chain amino acids in infants with maple syrup urine disease.  Arch Dermatol. 1993;129384- 385Google ScholarCrossref
Giacoia  GPBerry  GT Acrodermatitis enteropathica-like syndrome secondary to isoleucine deficiency during treatment of maple syrup urine disease.  AJDC. 1993;147954- 956Google Scholar
Goldblum  OMBrusilow  SWMaldonado  YAFarmer  ER Neonatal citrullinemia associated with cutaneous manifestations and arginine deficiency.  J Am Acad Dermatol. 1986;14321- 326Google ScholarCrossref