A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders

The average of blood ammonia levels at period of baseline, month 1, month 6, and every 6 months thereafter (1-5 years)

The maximum blood ammonia levels at period of baseline, month 1, month 3, month 6, and every 6 months thereafter (1-5 years)

The frequency of hyperammonaemic crisis at period of baseline, month 1, month 3, month 6, and every 6 months thereafter (1-5 years)

The change of height to the baseline in children aged 0-18 years old, and the proportion of weight in the upper, upper-middle, middle, lower-middle, and lower categories for each age group, according to the growth standards for children under 7 years old (WS/T 423-2022) and standard for height level classification among children and adolescents aged 7~18 years (WS/T 612-2018）issued by the National Health Commission of the People's Republic of China.

The change of weight to the baseline in children aged 0-7 years old, and the proportion of weight in the upper, upper-middle, middle, lower-middle, and lower categories for each age group, according to the growth standards for children under 7 years old issued by the National Health Commission of the People's Republic of China (WS/T 423-2022).

The change of head circumference to the baseline in children aged 0-3 years old, and the proportion of head circumference in the upper, upper-middle, middle, lower-middle, and lower categories for each age group, according to the growth standards for children under 7 years old issued by the National Health Commission of the People's Republic of China (WS/T 423-2022).

The changes of dose adjustment in glycerol phenylbutyrate throughout the study

The neonatal behavioral neurological assessment (NBNA) scale was used for newborn participants who were at least 2 months of age, consisting of 20 items, with a maximum score of 40 points. The total scores of the NBNA are derived from the cumulative sum of the scores obtained in behavioral ability (6 items), passive muscle tone (4 items), active muscle tone (4 items), primitive reflexes (3 items), and general assessment (3 items), which are collected according to the scales have been actually completed by the subjects in the clinical practice. The total scores greater than 37 is considered normal, while a score less than or equal to 37 is considered abnormal.

The Bayley Scale of Infant Development was used for infant participants whose ages range from 2 months to 30 months, consisting of 244 behavioral items, including 163 items on the mental scale and 81 items on the motor scale. The scores of each infant on the mental and motor scales are converted into standard scores with a mean of 100 and a standard deviation of 16 according to age groups, thereby calculating the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). A total score of MDI and PDI, which are collected according to the scales have been actually completed by the subjects in the clinical practice, are less than 70 indicates developmental delay, 70-79 indicates a borderline state, 80-89 indicates low average, 90-109 indicates average, 110-119 indicates high average, 120-129 indicates superior, and a score of 130 or above indicates very superior.

The assessment for Gesell Developmental Diagnosis Scale Scores was used for participants whose ages range from 30 months to 6 years, including five areas: gross motor skills, fine motor skills, adaptive behavior, language, and personal-social behavior. The observed behavioral patterns are identified based on the standard of normal behavioral patterns and are expressed in terms of age. This age is then compared with the actual age to calculate the Developmental Quotient (DQ), which is DQ = Developmental Age / Actual Age × 100, and the values of DQ are collected according to the scales have been actually completed by the subjects in the clinical practice. A DQ of 85 or above is considered normal for the nervous system, a DQ between 75 and 85 (inclusive of 75 but exclusive of 85) indicates a borderline level of nervous system impairment, and a DQ below 75 indicates nervous system damage.

The Chinese - Wechsler Preschool and Primary Scale of Intelligence (C - WYCSI) was used for children participants whose ages range from 4 to 6 years. The Verbal Intelligence Quotient (VIQ) test includes five subtests: Information, Picture Vocabulary, Arithmetic, Picture Comprehension, and Comprehension. The Performance Intelligence Quotient (PIQ) test includes five subtests: Animal Hatching, Picture Completion, Mazes, Geometric Shapes, and Block Design. The intelligence quotient (IQ) score obtained from the 10 subtests of VIQ and PIQ is the Full Intelligence Quotient (FIQ). The values for VIQ, PIQ and FIQ are collected according to the scales have been actually completed by the subjects in the clinical practice. FIQ is divided into five levels: ≥130 is superior, 116 - 129 is above average, 85 - 115 is average, 70 - 84 is below average, and < 70 is intellectual disability.

The Chinese-Wechsler intelligence scale of children (C-WISC）was used for participants whose ages range from 7 to 18 years. This scale consists of 11 subtests. The Verbal Intelligence Quotient (VIQ) test includes Information, Comprehension, Similarities, Arithmetic, Digit Span, and Vocabulary. The Performance Intelligence Quotient (PIQ) test includes Picture Completion, Picture Arrangement, Block Design, Object Assembly, and Coding. First, the raw score is calculated based on the test results of the examinee. Then, the corresponding age-specific scale score coefficient is checked and converted into a scale score. The sum of the VIQ and PIQ scale scores is the full intelligence quotient (FIQ) score, which are collected according to the scales have been actually completed by the subjects in the clinical practice. A FIQ of ≥120 is classified as high intelligence, 90-119 is classified as normal intelligence, and a score < 90 is classified as low intelligence.