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Picture of the Month
Masayuki Sasaki, MD;
Hiroshi Aikoh, MD;
Kenji Sugai, MD;
Hiroshi Yoshida, MD;
Walter W. Tunnessen, Jr, MD
From the Department of Child Neurology, National Center hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry (Drs Sasaki, Aikoh, and Sugai) and Department of Pediatrics, Shonai Hospital (Dr Yoshida), Tokyo, Japan; and the American Board of Pediatrics, Chapel Hill, NC (Dr Tunnessen).
Arch Pediatr Adolesc Med. 1998;152:707-708.
A 13-MONTH-OLD infant with methylmalonic acidemia presented with an erythematous, desquamating rash that had begun in the diaper area and progressively spread to involve parts of the face, extremities, and trunk (Figure 1 and Figure 2). As part of his treatment for methylmalonic acidemia, dietary protein was restricted (1.2 g/kg per day). Before the rash began, he had gastroenteritis and was not able to tolerate this diet for 3 days.
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Figure 1.
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Figure 2.
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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,4-6 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
AUTHOR INFORMATION
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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.
REFERENCES
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1. Fenton WA, Rosenberg LE. Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease. New York, NY: McGraw-Hill Book Co Inc; 1995:1423-1449.
2. Koopman RJJ, Happle R. Cutaneous manifestations of methylmalonic acidemia. Arch Dermatol Res. 1990;282:272-273.
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3. De Raeve L, De Meirleir L, Ramet J, Vandenplas Y, Gerlo E. Acrodermatitis enteropathica-like cutaneous lesions in organic aciduria. J Pediatr. 1994;124:416-420.
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4. Spraker MK, Helminski MA, Elsas LJ. Peri-orificial dermatitis secondary to deficiency of isoleucine in treated infants with maple syrup urine disease [abstract]. J Invest Dermatol. 1986;4:508.
5. Northrup H, Sigman ES, Hebert AA. Exfoliative erythroderma resulting from inadequate intake of branched-chain amino acids in infants with maple syrup urine disease. Arch Dermatol. 1993;129:384-385.
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6. Giacoia GP, Berry GT. Acrodermatitis enteropathica-like syndrome secondary to isoleucine deficiency during treatment of maple syrup urine disease. AJDC. 1993;147:954-956.
7. Goldblum OM, Brusilow SW, Maldonado YA, Farmer ER. Neonatal citrullinemia associated with cutaneous manifestations and arginine deficiency. J Am Acad Dermatol. 1986;14:321-326.
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SECTION EDITOR: WALTER W. TUNNESSEN, JR, MD
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