Case Description

The female infant was the fourth fetus and third delivery for the mother and was born by cesarean section at 36 weeks gestation, with a birth weight of 2.2 kg. Her amniotic fluid was clean at birth, and she was breastfed after birth. The father was healthy, and the mother was a carrier of chronic hepatitis B virus, and they were not close relatives. The mother's first child was aborted for personal reasons; the second child, a boy, died on the day of birth of an unknown cause. The third child, a 5-year-old girl, is in good health. The family pedigree is shown in Figure 4. After birth, the child was diagnosed as a premature infant and hospitalized for 13 days. When discharged from the hospital, the child's general condition was good, and she showed good feeding behavior and reflexes. However, weight gain was not ideal, and the child's body mass was only 3.66 kg at 2 months. At 61 days, she was admitted to another hospital for 1 day due to fever; her responses deteriorated, and she was transferred to our hospital for further treatment. A physical examination conducted upon admission revealed poor response, lethargy, shortness of breath, and low muscle strength and tone in the extremities. Routine laboratory tests showed that the patient had hypoglycemia (glucose: 0.28 mmol/L) and elevated myocardial enzymes [creatine kinase (CK): 569 U/L; CK-MB: 136 U/L] and transaminases (alanine aminotransferase: 169 U/L; aspartate aminotransferase: 239 U/L). Even after symptomatic treatments such as increasing blood sugar, nourishment of the heart, and protection of the liver, the patient's condition gradually deteriorated. Five hours after admission, apnea and cardiac arrest occurred, accompanied by low peripheral capillary oxygen saturation (70%); several resuscitation attempts failed, and the patient died.

Heel blood and urine samples were collected for tandem mass spectrometry (MS/MS) and gas chromatography–mass spectrometry analyses. All mass spectrometry experiments were performed on a Waters TQD mass spectrometer (Waters, Milford, Massachusetts, USA). Data were acquired and analyzed with Waters MassLynx v4.1 software. The urine samples were treated with urea removal, internal standard add, protein removal, vacuum drying, and trimethylsilyl derivatization and then analyzed by JMS-Q1000GC GC-MS (JEOL, Japan) for such as organic acids, amino acids, carbohydrate, polyols, purines, and pyrimidines in the urine. After the child died, we immediately biopsied her liver with the consent of her parents. Liver tissues were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned at 5 μm. Hematoxylin, eosin, Prussian blue, reticular fiber, masson, and picrosirius red staining were performed according to standard procedures.