479 - Effective Cystine Level Lowering with Oral Administration of Delayed-Release Cysteamine Bitartrate in Young Infants with Cystinosis

Publication Number: 2467.479

Mallory Mandel, Boston Children's Hospital, Boston, MA, United States; Avram Traum, Boston Children's Hospital, Boston, MA, United States; Deborah R.. Stein, Boston Children's Hospital, Brookline, MA, United States

Background: Nephropathic cystinosis is a rare metabolic disorder of cystine accumulation within lysosomes, leading to crystal formation and multiorgan damage, with kidneys especially vulnerable. Children develop signs of renal proximal tubular wasting between 6-12 months old with symptoms that include poor growth, metabolic acidosis, vomiting, polyuria, excessive thirst, dehydration, and hypophosphatemic rickets. Untreated, renal failure typically ensues by age 10. The advent of cystine-depleting therapy with cysteamine bitartrate has improved kidney survival and life expectancy though required dosing every 6 hours. The delayed-release (DR) formulation of cysteamine allows for improved compliance with twice-daily dosing and reduced gastrointestinal (GI) and sulfurous body odor side effects. Despite these improvements, children with cystinosis continue to struggle with significant GI challenges from underlying tissue inflammation, increased gastric acid production, decreased motility, and nausea from the cysteamine treatment itself. Some children require gastrostomy tube (G-tube) placement for administration of multiple medications and higher calorie and fluid requirements.

Objective: To describe the feasibility of target cystine level attainment with oral administration of DR cysteamine in infants with cystinosis.

Design/Methods: Case series describing 4 young patients with cystinosis receiving oral DR cysteamine.

Results: Case characteristics are summarized in Table 1. Age at diagnosis ranged from 3 to 27 months. DR cysteamine was taken orally with intact granules sprinkled onto foods such as applesauce, yogurt, and berry jelly, to prevent the medication's enteric coating from dissolving prior to its intended release in the small intestine. For improved tolerance, a low dose was initiated and gradually increased until target serum trough cystine levels (defined as < 1.9 nmol half-cystine/mg protein) were achieved. Target levels and acceptable growth trends were reached (Figures 1 and 2). No children required growth hormone.

Conclusion(s): Children with cystinosis can attain target cystine levels with orally administered DR cysteamine. Additionally, we report the first two cases in the literature of achieved target cystine levels in infants with treatment initiation before the age of one. This demonstration of successful therapy and growth is noteworthy as pre- and post-natal genetic testing continue to rise, allowing for earlier disease confirmation and treatment initiation. Placement of G-tubes should be tailored to each individual patient and not placed preemptively without a trial of oral medication tolerance.

Table 1: Case Summaries


Figure 1: HalfCystine Trough Levels Over Time After Delayed Release Cysteamine Initiation


Figure 2: Weight Trend Over Time
Pediatric weight percentiles per WHO child growth standards 0-2 years (in months) for Patients A and D, and per CDC growth standards 2-20 years (in years) for Patients B and C. Arrow depicts growth trend after treatment initiation for Patients A (15 months) and D (4 months), not shown for Patient B (10 months) and C (2 years).