A nine-month-old boy chiefly complained of vomiting and mental fatigue; these symptoms were reported to have lasted for half a day by the parents. The patient presented the following recent illness history: the day before admission, the child vomited stomach contents twice without obvious triggers and subsequently experienced mental fatigue and hypoglycemia. After half a day of outpatient treatment, the child remained mentally fatigued, with a poor response and reduced appetite. His parents denied any dietary complications. The patient was transferred to our hospital for further diagnosis and treatment. Since disease onset, the patient had experienced mental fatigue, decreased appetite, and poor sleep, although no significant change was observed in body weight. The patient's health and personal history were as follows: Birth history: G2P2, full-term vaginal delivery; birth weight 3.85 kg. (2) Newborn disease screening history: An newborn screening sample obtained on the third day after birth was reported to be elevations of C0, C6, C8, C10, C12, C14:1, and C14:2. (3) Feeding history: Breastfed for four months and post-formula fed until admission, with the gradual addition of complementary food from six months of age with no adverse reactions. (4) Growth and developmental history: Weight and height gradually increased, with laughing at two months, stable neck erection at three months, and turning over at five months; however, unstable neck erection was observed after admission at nine months. (5) Family history: Healthy parents and non-consanguineous marriages, although the patient's sibling exhibited abnormal screening results, poor overall health, and a low height and weight and was prone to colds. Physical examination showed that the body weight was 9.0 kg; height was 72 cm; the limbs were hypotonia; the patient's neck erection was unstable. He was unable to sit alone because the lower limbs could not support his body weight in the standing position. However, bilateral knee tendon and bilateral Achilles tendon reflexes were elicited symmetrically. No abnormal touch was found, physiological reflexes were present, and Bruchner's, Klinefelter's, and double Barthel's signs were all negative. The preliminary diagnosis was a suspected genetic metabolic disease.
Auxiliary examination revealed the following: (1) Color Doppler ultrasound: Hepatomegaly, 5.0 cm below the right rib, liver parenchyma echo enhancement; (2) blood routine test: WBC, 27.1 x 10*9/l; (3) biochemical examination: HCO3-, 14.2 mmol/L; TBA, 51.6 micromol/L; ALT, 110 U/L; AST, 250 U/L; GLU, 2.90 mmol/L; UA, 550 micromol/L; LDH, 429 U/L; and CK, 222 U/L; (4) urine organic acids: Glutaric acid, 2-hydroxyglutaric acid, 3-hydroxyglutaric acid, and other glutaric acid increased; (5) blood mass spectrometry screening: C0, C6, C8, C10, C12, C14:1, and C14:2 increased; (6) the remainder of the examinations, such as brain MRI and ECG, were all normal, as shown in Table 1. To confirm the diagnosis, peripheral blood samples were collected from the proband for WES.
After hospitalization, ceftazidime anti-infection, glutathione liver protection, and other treatments were all administered. According to the children's blood tandem mass spectrometry and urine organic acid results, late-onset MADD was considered a possibility, and in response, the patient was given large doses of vitamin B2 (50 mg, tid), levocarnitine (10 ml, oral tid), coenzyme Q10 (50 mg, tid). After 1 week, WES results confirmed our diagnosis. At the time of discharge, the patient appeared responsive and exhibited normative behavior for his age. However, the liver reached 3 cm below the ribs, and low muscle tone was observed in the limbs. Furthermore, unstable neck erection continued; the patient could not raise his head in the prone position, support the elbow, sit unsupported, and support the weight of the lower limbs in the standing position. Prescription of the doctor during discharge: Levocarnitine 3.33 ml, oral tid; vitamin B2 50 mg, tid; coenzyme Q10 50 mg, tid; compound glycyrrhizin half tablet tid; low-fat, low-protein, high-carbohydrate diet. Blood mass spectrometry and urinary organic acids were rechecked one week after hospitalization: C6, C8, C10, C10:1, C12, C14:1, and C14:2 all increased. Meanwhile, urinary organic acid results were normal.
After follow-up at six months, physical examination showed that body weight was 10.4 kg and height is 79 cm. He can sit alone, hold his head up, turn over, crawl, pronounce babamama, and walk a few steps alone. Muscle strength and muscle tone of the limbs were normal, physiological reflexes existed, and pathological signs were all negative. Auxiliary examination revealed C6, C8, C10, C10:1, C12, C14:1, and C14:2 all increased, however, urinary organic acids results remained normal.
After a subsequent follow-up at one year, physical examination showed that the weight was 11 kg, height was 88 cm, and he can walk alone and express simply. Blood tandem mass spectrometry showed that C6, C8, C10, C10:1, C12, C14:1, and C14:2 still increased.