Orthopaedic Problems in 35 Patients With Organic Acid Disorders

J Pediatr Orthop. 2021 Jul 1;41(6):e457-e463. doi: 10.1097/BPO.0000000000001812.


Introduction: Organic acid disorders (OADs) are a subset of inborn errors of metabolism that result in a toxic accumulation of organic acids in the body, which can lead to metabolic derangements and encephalopathy. Patients with these disorders are managed by a team of biochemical geneticists and metabolic nutritionists. However, subspecialists such as neurologists and orthopaedic surgeons are often needed to help manage the sequelae of the metabolic derangements. The breadth of orthopaedic sequelae of these disease states is poorly understood. Herein, we describe orthopaedic problems associated with 5 types of OAD most commonly seen at our institution: maple syrup urine disease, methylmalonic aciduria, propionic aciduria, pyruvate dehydrogenase deficiency, and glutaric aciduria type 1.

Methods: We retrospectively reviewed medical records of 35 patients with an OAD who were seen at our academic tertiary care center from May 1999 to May 2020. Patients were grouped into cohorts according to OAD type and analyzed for orthopaedic presentations of hip, knee, or foot disorders, presence and severity of scoliosis, history of fracture, movement disorders, and osteopenia/osteoporosis.

Results: Of the 35 patients, 13 had maple syrup urine disease, 12 had methylmalonic aciduria, 4 had propionic aciduria, 4 had pyruvate dehydrogenase deficiency, and 2 had glutaric aciduria type 1. Associated orthopaedic problems included spasticity causing neuromuscular scoliosis and/or hip subluxation or dislocation (10 patients), fractures (7 patients), and osteopenia/osteoporosis (7 patients). Overall, 22 of 35 patients had some orthopaedic condition.

Conclusions: Most in this cohort of patients with OAD also had an orthopaedic abnormality. It is important for physicians treating these patients to understand their propensity for musculoskeletal problems. When treating patients with OAD, it is important to initiate and maintain communication with specialists in several disciplines and to develop collaborative treatments for this unique population.

Level of evidence: Level IV-prognostic study.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Metabolism, Inborn Errors / complications
  • Brain Diseases, Metabolic / complications
  • Child
  • Child, Preschool
  • Female
  • Glutaryl-CoA Dehydrogenase / deficiency
  • Humans
  • Male
  • Maple Syrup Urine Disease / complications
  • Maple Syrup Urine Disease / surgery
  • Middle Aged
  • Orthopedics*
  • Propionic Acidemia / complications*
  • Propionic Acidemia / surgery*
  • Pyruvate Dehydrogenase Complex Deficiency Disease / complications
  • Pyruvate Dehydrogenase Complex Deficiency Disease / surgery
  • Retrospective Studies


  • Glutaryl-CoA Dehydrogenase

Supplementary concepts

  • Glutaric Acidemia I
  • Methylmalonic acidemia