RESUMO
Objective:To investigate the clinical features, treatment, and prognosis of transient hyperammonemia of the newborn (THAN).Methods:Data of two infants with severe THAN admitted to the Department of Neonatology of Shanghai Children's Hospital in September 2021 and August 2022 were retrospectively investigated. Clinical data of confirmed THAN cases (blood ammonia>400 μmol/L) were collected from relevant literature retrieved from the Wanfang Database, China National Knowledge Infrastructure, Chinese Medical Journal Database, and PubMed up to July 2022. A descriptive method was used for statistical analysis.Results:A total of 24 cases were involved (two in the present study, and 22 in 12 retrieved articles), including 19 (79.2%) premature newborns and five term infants. The average birth weight was (2 237±608) g and the average onset time was 27 h (4-55 h) after birth. The early clinical symptoms included respiratory distress and hyporesponsiveness (drowsiness, lethargy, coma or hypotonia) in 18 cases (75.0%), metabolic acidosis in 11 cases (45.8%), hypocalcemia in seven cases (29.2%), pupil fixation/dilation in six cases (25.0%), convulsion in five cases (20.8%), apnea in three cases (12.5%) and sinus bradycardia in one case (4.2%). The serum ammonia levels were 1 422.8 μmol/L (547.2-4 494.1 μmol/L). Treatments included peritoneal dialysis plus exchange transfusion in eight cases (33.3%), exchange transfusion in seven cases (29.2%), continuous renal replacement therapy (CRRT) in four cases (16.7%), arginine in two cases (8.3%), peritoneal dialysis in two cases (8.3%), and CRRT+peritoneal dialysis in one case (4.2%). During follow-ups of four months (one month to six years), 13 cases (54.2%) showed no abnormalities in development; two (8.3%) had a neurodevelopmental delay, and six (25.0%) died. The follow-up of the other three cases (12.5%) were not reported in the literature.Conclusions:The early clinical manifestation of severe THAN is atypical. A good prognosis can be expected through early exclusion of possible hyperammonemia-related genetic metabolic diseases and lowering the serum ammonia level. Long-term follow-up is needed for neurological evaluation.
RESUMO
Objective:To investigate the clinical and molecular genetic features of neonatal congenital Netherton syndrome (NS) caused by mutations in serine protease inhibitor of Kazal type 5 ( SPINK5) gene. Methods:This study retrospectively analyzed the clinical data of an NS neonate admitted to Shanghai Children's Hospital in November 2018. SPINK5 gene was analyzed using high-throughput sequencing and Sanger sequencing. Relevant articles were retrieved from various databases including China National Knowledge Infrastructure, Wanfang and PubMed, and the reported cases who were diagnosed as NS within two months after birth with SPINK5 gene sequencing results were reviewed. Clinical features, gene mutations, treatment and follow-up results of NS were summarized using descriptive statistical analysis. Results:The patient presented with diffuse erythema and desquamation, sparse hair and repeated infections shortly after birth. Laboratory tests revealed elevated IgE (111 IU/ml) and "invagination-like" change in the hair under optical microscope. SPINK5 gene analysis found that there were compound heterozygous mutations of c.2468dup (p.Lys824Glufs*4) and c.377_378del (p.Tys126*) in the child. The pedigree analysis found that the two mutations were respectively inherited from the father and the mother, which supported the diagnosis of NS caused by SPINK5 gene mutation. Though skin rash improved after comprehensive treatments including anti-infection therapy, gamma globulin injection and skincare, the patient suffered from recurrent infection and was discharged from the hospital after giving up treatment and died of infection at two months old. Eleven NS cases were retrieved from literature and altogether 12 cases were analyzed here. The most common clinical manifestations in the 12 patients were early skin diffuse erythema and desquamation (12/12), infection (8/12), dry hair (7/12), hypernatremia dehydration (7/12), high IgE (5/12), growth retardation (4/12), respiratory failure (3/12), atopic constitution (2/12), diarrhea (2/12), dysphagia (1/12), hypothermia (1/12), wheezing (1/12), hypertension (1/12), liver failure (1/12) and metabolic alkalosis (1/12). Conclusions:NS is caused by SPINK5 gene mutation with atypical manifestations in neonates. Neonates with diffuse erythema and desquamation of the skin, repeated infections, dry hair and especially with high blood IgE should be considered the possibility of NS. Genetic testing is conducive to early diagnosis, guiding treatment decisions and providing a basis for genetic counseling.