posted 12-05-2006 08:53 PM            

Program Nr: 2413
Co-incidence of PKU and propionic acidemia in an Amish girl. S.E. McCandless1,3, J.W. McConnell2, D.S. Kerr2. 1) Dept of Pediatrics, Univ of North Carolina; 2) Rainbow Babies and Children's Hosp, and; 3) Dept of Genetics, Univ Hospitals of Cleveland/Case Western Reserve Univ.

Propionic acidemia (PA) was recently diagnosed in an Amish female infant in whom PKU had been diagnosed by routine newborn screening (initial phe concentration 38 mg/dl). In addition to products of phe metabolism, methylcitrate and tiglylglycine were unexpectedly found in the urine organic acid analysis. Plasma and urine contained large amounts of propionylcarnitine. Enzyme analysis (fibroblasts) demonstrated very low propionyl-CoA carboxylase activity with normal activity of pyruvate and methylcrotonyl-CoA carboxylases. Urine pteridines were normal, as were serum biotinidase and RBC dihydropteridine reductase activities. At age 2 months, prior to treatment, she developed vomiting, decreased appetite and irritability, with metabolic acidosis and hyperammonemia (155mM). •• Management required combining two different amino-acid restricted formulas and oral carnitine (50 mg/kg/day). With treatment, phe was typically 2-6 mg/dl. At 6 months of age growth and development were normal. During this time of rapid growth the combination of the 2 formulas has met her requirements for essential amino acids without causing significant accumulation of phe or metabolites of propionyl-CoA. ••• There were several individuals with PKU on both sides of the family, but no recognized cases of PA nor consanguinity in the 4-generation pedigree. A 2-year-old sister of the proband with hypotonia and global developmental delay was tested and found to have PA but not PKU. That child had no episodes of serious illness, coma, blood dyscrasias or acidosis. •••• We are not aware of previous reports of co-incidence of these two rare metabolic diseases. This case alerts physicians to the possibility that rare genetic disorders may co-exist in a member of an in-bred group. The use of broader confirmatory testing enabled subclinical detection of PA in this case, and raises awareness of the usefulness of broader newborn screening, particularly in in-bred populations. The combined restriction of phe and propiogenic amino acids has been workable and effective, resulting in normal growth and development to date.

Janice S. Boecker
Research Director
Propionic Acidemia Research Network (PARnet)
jsboecker@paresearch.org www.paresearch.org
512-394-0977