MSUD is a an inborn error of metabolism resulting from a deficiency of a mitochondrial enzyme known as branched- chain alpha ketoacid dehydrogenase , this enzyme is important for the decarboxylation of the following amino acids: leucine, isoleucine and valine. The dificiency of this enzyme leads to elevated levels of leucine, isoleucine and valine in body fluids especially urine, giving it its' ⁷ characteristic odor of maple syrup, hence the name of this disease. Management of MSUD in the acute state is aimed at quick removal of the accumualted branched chain amino acids, leucine,isoleucine and valine as well as their metabolites from the tissues and body fluids and this is usually established by peritoneal dialysis,  the patient should also be provided with  sufficient calories either orally or if not tolerated intravenously so as to prevent increased catabolic states.⁷During the recovery from the acute states, the patient should be kept on special formulas that are devoid of these branched chain amino acids, but small amounts of these amino acids should be added to the diet as these amino acids are not synthesized endogenously, and follow up by frequent analysis of plasma amino acids should be done. If levels of isoleucine fall too low in children who are kept on this restricted diet, and particularly during increased catabolic states as in infections, a skin eruption resembling acrodermatitis enteropathica  develops. Recovery is quick and complete after the addition of isoleucine or the other deficient amino acids to the diet ³.

CASE REPORT

Here described is a 3 year old saudi girl with classic MSUD who was admitted to the pediatric ICU as a case of pyrexia of unknown origin with respiratory distress, anemia, and diarrhea , her treatment consisted of IV fluid hydration,  antibiotics, packed RBCs transfusion and anticonvulsant drugs. She was kept on a restricted diet devoid of branched chain amino acids. During her ICU admission, she developed a skin eruption that involved the acral parts of her body, periorificial areas and the napkin area.The skin eruption began as  erythematous macules  which were followed by erosions distributed on the hands , feet, face and the napkin area. The skin seemed to be fragile as any attempt for blood withdrawal resulted in erosions at the site of needle pricks.Differential diagnosis at this stage included staphylococcal scalded skin syndrome, toxic epidermal necrolysis , drug eruption, a blistering disease, acrodermatitis enteropathica , and acrodermamtitis enteropathica like eruption due to isoleucine  and /or leucine deficiency.Skin swabs done grew enterobacter cloacae and enterobacter faecalis, both were covered with the appropriate antibiotic according to culture and sensitivity.Biopsy showed mild acanthosis, focal parakeratosis and epidermal ulceration, dermal tissue showed superficial perivascular mononuclear inflammatory infilterate. Immunofluorscent studies yeilded negative results for IgA, IgG, IgM, and C3.Unfortunately amino acid assays were not available to confirm the diagnosis of acrodermatitis enteropathica like eruption nor was  zinc level  , but a trial of isoleucine and luecine supplementation was done, and resulted in rapid recovery of the skin lesions, confirming our suspicions that this eruption may be due to branched chain amino acid deficiency.Conditions similar to acrodermatitis enteropathica may also develop in other states including nutritional deficiencies such as essential fatty acid deficiency ,kwashiorkor, biotin deficiency , amino acid deficiencies ¹ as in our case which was iatrogenically induced by keeping the patient on a  branched chain amino acid free formula without supplementation, similar eruptions can also occur in prolonged parentral nutrition without zinc supplementation , as well as in burns , trauma , nephrotic syndrome, cystic fibrosis , and AIDS ¹.  In conclusion, the patient described here most probably has acrodermatitis enteropathica like eruption which is most likely iatrogenically induced through keeping the patient on a branched chain amino acid free formula without supplementation of the deficient amino acids especially at times of increased catabolic states as in infections, as evidenced by the prompt response to isoleucine and leucine supplementation that has resulted in quick recovery of the skin lesions.^3,4,5,8Upon reviewing the literature no clear pathogenesis was ever described , but branched chain amino acids may be essential for normal growth and differentiation of keratinocytes ².                           

Figure 1. Erosion of Anogenital Area

Figure 2.  Eczematous crusted lesions around and at the angles of the mouth.                    

Figure 3.  Hand Erosion                    

Figure 4. Erosion of Feets

Figure 5. Resolving of erosions on the 5^th day after starting supplementation with the deficient amino acids     

REFERENCES

1. Baker H. Al Awamy, Mohammed S Al-Madan, cutaneous lesions during dietetic therapy in patients with maple syrup urine disease, Kuwait medical journal 2002,34 (3): 224-226.
2. TemplierI. Reymond JL,Nguyen MA, Boujet C, Lantuejoul S, acrodermatitis enteropathica like syndrome secondary to branched –chain amino acid deficiency during treatment of maple syrup urine disease, Ann dermatol Venereol,  2006 April; 133(4): 375-9.
3. Giacoia, GP, Berry GT, Acrodermatitis enteropathica- like syndrome secondary to isoleucine deficiency during treatment of maple syrup urine disease. Am J Dis Child.1993 Sep; 147 (9): 954-6.
4. Tain YL, Huang SC, Hung FC, Wang HS, Sun PC, Acrodermatitis enteropathica –like eruption during treatment of maple syrup urine disease : report of one case.
5. Puzenat E, Durbise E, Fromentin C, Humbert p, Aubin F, iatrogenic acrodermatitis enteropathica-like syndrome in leucinosis, Ann Dermatol Venereol, 2004 Aug-Sep; 131(8-9): 801-4.
6. Fitzpatrick, Dermatology in general medicine, volume 2 , fifth edition 1999, pages 1738-1740.
7. Nelson , Textbook of pediatrics, fourteenth edition, 1992, pages 316-318.
8. Masayuki Sasaki, MD; Hiroshi Aikoh,MD, et al. Cutaneous lesions associated with Isoleucine deficiency.