Musculoskeletal manifestations of neonatal nonketotic hyperglycinemia

Abstract

Purpose Neonatal nonketotic hyperglycinemia is an autosomal recessive inborn disorder of glycine metabolism in which large quantities of glycine accumulate in all body tissues. It is characterized by a progressive lethargy, hypotonia, myoclonic jerks, and early death secondary to respiratory problems. As a result of early diagnosis and treatment protocols, more patients survive the critical neonatal period with profound mental retardation, delayed developmental milestones, seizures, and spasticity. There are no reports about the orthopaedic manifestations of neonatal nonketotic hyperglycinemia. The purpose of this study is to evaluate the musculoskeletal findings of neonatal nonketotic hyperglycinemia. Methods This is a retrospective IRB-approved study of all patients in our Orthopaedic and Genetics Clinics with the diagnosis of neonatal nonketotic hyperglycinemia during a 10-year period. Demographic, clinical, and imaging data were analyzed. Results Twelve patients with neonatal nonketotic hyperglycinemia were evaluated, with a mean age of 7 years and 2 months (range: 5 months to 21 years). Seven were male and five were female. Eleven patients (92 %) have evidence of progressive early-onset neuromuscular scoliosis with a mean Cobb angle of 55°(range: 30-95°). Five children (42 %) presented evidence of progressive hip dislocation secondary to spasticity. All the patients have severe multiple joint contractures. Conclusion Neonatal nonketotic hyperglycinemia is a rare metabolic disorder presented in the past as a lethal condition. Recent advances in early diagnosis and neonatal care improve overall outcome. As pediatric orthopaedic surgeons, we need to establish treatment based on update information of the disease and probability to improve quality of life.

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis

“…Homozygous mutations in the SLC6A9 gene that encodes GLYT1 cause glycine encephalopathy, also known as nonketotic hyperglycinemia (NKH), which is a severe neurological disease caused by abnormally high levels of glycine in the cerebrospinal fluid (CSF) and characterized by respiratory failure, progressive hypotonia, and startle-like reflexes (24,25). Interestingly, although most glycine encephalopathy patients die before 7 months of age, those who survive show progressive early onset scoliosis as a result of apparent neurological defects (26)(27)(28).…”

Nonketotic Hyperglycinemia: Insight into Current Therapies

“…Another complication of NKH is the occurrence of musculoskeletal disorders, resulting from CNS dysfunction [ 4 , 47 ]. Severe multiple joint contractures that limit mobility or progressive neuromuscular scoliosis of early onset and painful dislocations of the hip joints are particularly common.…”

“…Severe multiple joint contractures that limit mobility or progressive neuromuscular scoliosis of early onset and painful dislocations of the hip joints are particularly common. Patients with orthopedic disorders are also at risk of developing thoracic failure syndrome [ 47 ].…”

Manejo anestésico en paciente pediátrico con hiperglicinemia no cetósica

“…Alrededor de 80% de los pacientes con HNC, presentan defectos en la proteína P y 15% sobre la T; la deficiencia de la H es un mecanismo desencadenante poco frecuente dentro de esta patología. [1][2][3] La presentación clínica clásica de la HNC aparece durante el período neonatal, caracterizado por hipotonía severa, apnea, letargia y convulsiones de difícil tratamiento. Sin embargo, existen presentaciones atípicas que ocurren en diferentes momentos de la infancia.…”

“…Dentro de las manifestaciones clínicas se encuentran convulsiones, trastornos de la alimentación, movimientos desorganizados, paraplejia espástica, lesión espinal, leucodistrofia, cardiomiopatía y atrofia óptica, entre otras. [1][2][3][4] Los pacientes con HNC presentan un mayor riesgo anestésico, pues la insuficiencia respiratoria, hipotonía generalizada, alteraciones en la succión y convulsiones refractarias, aumentan la probabilidad de desenlaces perioperatorios insastisfactorios. 5,6 Al corresponder a una enfermedad huérfana, la literatura disponible es escasa, por lo cual es importante el reporte de este caso.…”