Neuromuscular conditions and the impact of cystine-depleting therapy in infantile nephropathic cystinosis: A cross-sectional analysis of 55 patients

J Inherit Metab Dis. 2022 Mar;45(2):183-191. doi: 10.1002/jimd.12464. Epub 2022 Jan 13.

Abstract

Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disease caused by biallelic mutations in the cystinosin gene, leading to cystine accumulation in various organs. The aim of this cross-sectional study was to investigate neuromuscular complications in a cohort of 55 patients (aged 2.8-41.3 years, median 18.5 years) with INC. Clinical examination, jumping mechanography, clinical neurophysiology, and muscle/nerve ultrasound were performed. Physical performance, measured by mechanography, was below average in all patients. However, this reduction in physical performance was not always detected by conventional muscle power assessment. Twenty-eight percent of patients had mostly mild axial weakness of the neck flexors and/or of the abdominal rectus muscles, the latter often presenting during childhood. One adult patient had generalized muscle weakness. Two patients had evidence of specific neuromuscular conditions, which may not have been directly related to cystinosis. 30% of patients presented with mild, 7% with moderate, and 5% with severe weakness of the intrinsic muscles of the hand. Muscle wasting was more pronounced in the older cystinosis patients with multiple organ complications. Sonographic increase in muscle echogenicity corresponded only with severe weakness. Electromyography of the intrinsic hand muscles, performed in selected patients, showed myopathic, neurogenic, or mixed myopathic-neurogenic abnormalities. A particularly important finding of this study is that the neuromuscular complications were largely independent from both the age of initiation of pharmacological cystine-depleting therapy and from adherence to treatment. Significant correlation was observed between better physical performance in jumping and cysteine levels in leukocytes.

Keywords: Esslinger Fitness Index; distal myopathy; infantile nephropathic cystinosis; median nerve; neuromuscular complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Cysteamine / therapeutic use
  • Cystine
  • Cystinosis* / complications
  • Humans
  • Neuromuscular Diseases*

Substances

  • Cystine
  • Cysteamine

Supplementary concepts

  • Cystinosis, Infantile Nephropathic