Children, female, born in November 2020. One month after birth, she developed yellow skin, white stool, vomiting and diarrhea without any inducment, and was diagnosed as "hyperbilirubinemia" in a local hospital. At 3 months of age, amino acid and acylcarnitine analysis in blood, organic acid analysis in urine and gene detection indicated " Citrin deficiency and Turner syndrome ". She weighed 2.85kg at birth, 3.15kg at 1 month, 3.6kg at 2 months, 4.0kg at 3 months, 4.8kg at 4 months, 5.4kg at 19 days of May, and 55cm (< 3rd), 1 year old height 67cm, weight 7.5kg, head circumference: 43.3cm, 1 year and 3 months old physical examination: 74cm, weight 10kg, head circumference: 43.3cm. Physical examination at 2 years and 6 months: height 85cm, weight 13kg. There is no similar patient in the family and she has normal intelligence. She is currently on a low-carb diet and is treated with a small white peptide.
Ultrasound of the kidney at 3 months of age showed that the size of the right kidney was about 68.3×24.6mm, and the assembling system was divided into upper and lower parts. The diameter before and after separation of the upper pelvis was about 12.7mm, and the parenchymal echo was slightly thinner and about 2-3mm thick. No obvious separation was observed in the lower assembling system, and the parenchymal echo was evenly distributed. The size of the left kidney was about 52.5×20.5mm. No obvious abnormalities were observed in the position, shape and size of the kidney. The contour was clear, the parenchymal echo was evenly distributed, and there was no obvious separation and strong echo mass in the gathering system. Ultrasound of the kidney at 8 months of age showed that the size of the right kidney was about 72.4×23.9mm, and the collecting system was divided into upper and lower parts. The diameter before and after separation of the upper pelvis was about 12.8mm, and the parenchymal echo became thinner. No obvious separation was observed in the lower collection system, and the parenchymal echo was evenly distributed. Now, the full length of the right upper ureter is tortuosity and dilatation. The internal meridian of the middle and upper segment is about 8.2mm. The internal meridian of the posterior segment of the bladder wall is about 9.8mm. There is a somaticity in the bladder, about 12.5x11.7mm, which is connected to the dilated ureter. At 1 year and 10 months of age, B-ultrasound showed that the size of the right kidney was about 72.7×24.3mm, and the aggregate system was divided into upper and lower parts. The diameter before and after separation of the upper pelvis was about 8.8mm, and the parenchymal echo was reasonable, while no obvious separation was observed in the lower aggregate system, and the parenchymal echo was evenly distributed. The right upper ureter was tortuous and dilated all the way, with an internal meridian of about 5.7mm in the upper segment and 8.5mm in the posterior segment of the bladder wall. At 2 years and 4 months of age, B-ultrasound showed that the size of the right kidney was about 68.9×23.3mm, and the aggregate system was divided into upper and lower parts. The diameter before and after separation of the upper pelvis was about 7.0mm, and the parenchymal echo was reasonable, while no obvious separation was observed in the lower aggregate system, and the parenchymal echo was evenly distributed.
Results of blood amino acid and acylcarnitine metabolism: methionine 68.62µmol/L, tyrosine 122.55µmol/L, tetracylcarnitine 0.34µmol/L, hexadecylcarnitine 3.54µmol/L, octadecylcarnitine 0.95µmol/L at 4 months of age. Methionine 16.51µmol/L, tyrosine 78.16µmol/L, free carnitine 69.66µmol/L, cetacylcarnitine 2.37µmol/L at 9 months of age. At 21 months of age, methionine 16.49µmol/L, tyrosine 88.52µmol/L, free carnitine 47.57µmol/L, cetacylcarnitine 1.32µmol/L. At 2 years and 3 months of age, methionine 13.62µmol/L, tyrosine 42.76µmol/L, free carnitine 19.10µmol/L, cetacylcarnitine 0.90µmol/L.
Urinary organic acid results: 4-hydroxyphenylacetic acid 177.4, 4-hydroxyphenyllactic acid 1812, 4-hydroxyphenylpyruvate 230.2 at 4 months of age. At 21 months of age, 4-hydroxyphenylacetic acid was 35.7, 4-hydroxyphenyllactic acid 3.8, and 4-hydroxyphenylpyruvate 1.9. At 2 years and 4 months of age, 4-hydroxyphenylacetic acid 25.8, 4-hydroxyphenyllactic acid 5.2, 4-hydroxyphenylpyruvic acid 5.8.
Results of liver and kidney function: total bilirubin 220.8µmol/L, direct bilirubin 175.2µmol/L, indirect bilirubin 45.6µmol/L, alanine aminotransferase 526.6U/L, oxalacetic aminotransferase 977.4U/L, total bile acid 261.7µmol/L, alkaline phosphatase 431.5U/L at 4 months of age. Total bilirubin 22.0µmol/L, alanine aminotransferase 167.6U/L, aspartate aminotransferase 199.2U/L, uric acid 281.6µmol/L at 9 months of age. At 12 months of age, total bilirubin was 1.9µmol/L, alanine aminotransferase was 34.7U/L, oxalacetic aminotransferase was 48.5U/L and uric acid was 416.6µmol/L. At 21 months of age, total bilirubin was 3.6µmol/L, alanine aminotransferase was 27.6U/L, oxalacetic aminotransferase was 40.3U/L and uric acid was 343.7µmol/L. At 2 years and 4 months of age, total bilirubin was 5.8µmol/L, alanine aminotransferase was 51.6U/L, aspartate aminotransferase was 63.1U/L and uric acid was 437.5µmol/L.
Postnatal genetic testing results of the child showed (Fig. 1) : SLC25A13 complex heterozygous mutation (NM_001160210), mutation site: c.852-855del (p.R284fs) (heterozygous, from the mother), mutation site: c.1625C > A (p.A542D) (heterozygous, from father), suggesting "neonatal onset citrullinemia type 2". Further chromosome aneuploidy and genome copy number variation (CNVs) over 100Kb were performed in the child, and the results showed seq[hg19]del(X)(p22.33q28) chrX:g.1_155270560del (Fig. 2).