Congenital adrenal hyperplasia with maple syrup urine disease: An example of consanguinity impact.

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino acids (BCAAs) in plasma, α-ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine. The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. Clinical outcomes are generally good in patients where treatment is initiated early. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients.

The outcome of 12 children with classical maple syrup urine disease is reviewed. All patients presented in the neonatal period at ages varying from 5 to 21 (median 8) days. The time taken to make the diagnosis ranged from 1 day to longer than 9 months (median 7 days). Each survived his initial illness but 3 died later after apparently mild infections. Three of the 12 patients had a spastic quadriplegia and 6 others abnormal neurological signs without clear cerebral palsy. The single most important factor determining the outcome appears to be the time taken to make the diagnosis after the first symptoms. Two patients were diagnosed within 24 hours of the first symptoms and one is of above average ability. The other is mildly retarded but control of the disease was poor in his first 4 years of life. Outcome is unpredictable if the delay is between 3 and 14 days. Two children are of normal ability but 6 others are retarded. A delay longer than 14 days is invariably associated with mental retardation and cerebral palsy. We conclude that early diagnosis is essential to improve the outcome of this condition.