Chinese Male Infant Research Articles

Delayed diagnosis of complex glycerol kinase deficiency in a Chinese male infant: a case report

BackgroundXp21 contiguous gene deletion syndrome is a rare genetic metabolic disorder with poor prognosis in infants, involving deletions of one or more genes in Xp21. When deletions of adrenal hypoplasia (AHC), Duchenne muscular dystrophy (DMD), and chronic granulomatosis (CGD) loci are included, complex glycerol kinase deficiency (CGKD) can be diagnosed. We present a case of CGKD that was initially misdiagnosed and died during treatment in our hospital in terms of improving our understanding of the clinical features and diagnosis of this disease, as well as highlighting the need for more precise dosing of corticosteroid replacement therapy.Case presentationA 48-day-old full-term male infant was transferred to our medical center with global growth delay and persistent vomiting. Routine laboratory tests revealed hyperkalemia, hyponatremia, and a high level of creatine kinase. The initial diagnosis was adrenal cortical hyperplasia (ACH), then revised to adrenocortical insufficiency with a normal level of ACTH detected. After supplementing the routine lipid test and urinary glycerol test, CGKD was diagnosed clinically due to positive triglyceridemia and urinary glycerol, and the follow-up gene screening further confirmed the diagnosis. The boy kept thriving after corticosteroid replacement and salt supplementation. While levels of serum ACTH and cortisol decreased and remained low after corticosteroid replacement was administered. The patient died of acute type 2 respiratory failure and hypoglycemia after an acute upper respiratory tract infection, which may be the result of adrenal crisis after infection. Infants with CGKD have a poor prognosis, so physicians should administer regular follow-ups, and parents counseling during treatment to improve the survival of patients.ConclusionsOverall, CGKD, although rare, cannot be easily excluded in children with persistent vomiting. Extensive blood tests can help to detect abnormal indicators. Adrenal crisis needs to be avoided as much as possible during corticosteroid replacement therapy.

Successful treatment of an infant with congenital bile acid synthesis disorder type 3 by ursodeoxycholic acid: a case report

BackgroundCongenital bile acid synthesis disorder type 3 caused by oxysterol 7α-hydroxylase deficiency is an extremely rare genetic liver disease. As it may cause rapid progression to end-stage liver disease, a high cautiousness in diagnosis and early treatment are required. Here we describe the first case of congenital bile acid synthesis disorder type 3 in China that was confirmed by genetic analysis.Case presentationA 5-month-old Chinese male infant suffered skin yellowing since birth. The patient showed significantly increased alanine transaminase, aspartate transaminase, and total and direct bilirubin levels, and enlarged liver at admission. Whole-exome sequencing confirmed homozygous mutation in the CYB7B1 gene that encodes oxysterol 7α-hydroxylase. Ursodeoxycholic acid treatment significantly mitigated the condition of the patient and lowered biochemical indicators. Unfortunately, the patient developed septicemia and gave up treatment.ConclusionsThe patient was successfully treated with ursodeoxycholic acid, which has not been reported previously. Ursodeoxycholic acid replacement therapy is an effective and affordable treatment for congenital bile acid synthesis disorder type 3 caused by oxysterol 7α-hydroxylase deficiency.

Analysis of novel heterozygous mutations in the CYP11B2 gene causing congenital aldosterone synthase deficiency and literature review

Aldosterone synthase deficiency (ASD) is a rare autosomal recessive disorder characterized by severe hyperkalemia, salt loss, vomiting, severe dehydration and failure to thrive. ASD is a life-threatening electrolyte imbalance in infants resulting from mutations in CYP11B2. We described ASD in a Chinese male infant with vomiting, poor feeding and failure to thrive. He was mildly dehydrated, with a weight of 6 kg (−3.45 SDS) and length of 67 cm (−3.10 SDS). Laboratory tests showed hyponatremia (119 mmol/L), serum potassium 5.4 mmol/L, low plasma aldosterone and plasma renin activity (PRA) levels. Next-generation sequencing of his DNA revealed compound heterozygous mutations in CYP11B2, a known variant c.1391_1393delTGC (p.Leu464del, rs776404064) and a novel variant c.1294delA (p.Arg432Glyfs*37). The HEK-293T expression system was used to investigate the variants, demonstrating negligible aldosterone synthesis compared with WT CYP11B2. The patient started fludrocortisone and subsequently gained 3.2 kg of weight and normalized serum sodium (137 mmol/L). We further reviewed reported cases of ASD, summarizing clinical features and CYP11B2 mutations; missense and nonsense mutations are most frequent. Fludrocortisone treatment is essential for ASD, and the need for mineralocorticoid replacement wanes with age; eventually, therapy can be discontinued for many affected children. Our study broadens the ASD phenotypic spectrum and shows the efficiency of next-generation sequencing for patients with atypical clinical manifestations.

A novel site mutation in a wiskott-aldrich syndrome boy: A case report

Introduction: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immunodeficiency caused by WASP mutations. Identification of novel WASP mutations may help understand uncovered pathogenesis. We here noticed a rare case with a novel WASP mutation, which was also detected in his mother and grandmother. This article aimed to detect the genetic features of a WAS family and determine the source of the completely new mutation. Case presentation: This Chinese male infant was admitted to our department at postnatal day 7. He was found thrombocytopenia for 4 days. The family history documented that his two uncles both died in infancy due to repeated infections; his aunt had experienced 2 pregnancies, and both resulted in unexplained abortion. After 18-day treatment, his parents signed the request to discharge. The infant finally died at 9 months old. A novel heterozygous mutation in the exon 9 was found on his X chromosome, that c.928C>T resulting in amino acid changes p.Q310X. This mutation was revealed to be derived from his grandmother to his mother. Conclusion: In conclusion, a novel mutation (c.928C>T) was found in our male infant patient, as well as his mother and grandmother. The patient died from uncontrollable WAS symptoms, as the two boys of his grandmother did. Early detection and diagnosis of new mutation may reduce complications and increase the life expectancy of WAS patients. Prenatal DNA sequencing could be recommended to avoid birth of WAS in particular for male fetuses.

Severe microphthalmos with cyst and unusually huge dermolipoma.

The purpose of this study was to report an unusual case of severe microphthalmos, together with an orbital cyst and huge ocular surface dermolipoma. This is a clinical report relating clinical features as well as imaging and histopathologic findings, along with surgical management of the patient. A 5-month-old Chinese male infant was referred, with 2 large masses in the left eye that were present since birth. Ocular examination results revealed a complete absence of any eye structures in the left orbit. In its place were 2 large masses between the left upper and lower palpebral fissure. One was a 3 × 3 × 2.5-cm spherical red tumor with a smooth surface. The other was a large solid spherical tumor, 4 × 4 × 5 cm, covered with normal skin located in the temporal region and attached to the red mass by a pedicle. Orbital magnetic resonance imaging examination findings confirmed that no eye structures were present in the left orbit. However, a cystic lesion was found in the left orbit, with a low signal on T1-weighted imaging and high signal on T2-weighted imaging, and another huge spherical heterogeneous mass was located "outside" the left orbit. Anterior orbitotomy by conjunctival incision was performed under general anesthesia. A spherical cystic mass of 1.5 × 1.5 × 1.6 cm, a small eye of 0.7 × 0.7 × 0.6 cm, and a huge dermolipoma were removed completely. Pathologic examination results confirmed the diagnosis of severe microphthalmos, together with orbital dermoid cyst and dermolipoma. This rare case demonstrates that severe microphthalmos with a cyst may be completely covered by conjunctiva and associated with an unusually huge dermolipoma.

Analysis of OCRL gene mutation in a male infant with Lowe syndrome

To identify pathological mutation in a Chinese male infant featuring oculocerebrorenal syndrome (also called Lowe syndrome). Clinical data of the patient were collected. DNA was extracted from peripheral blood of the infant and his parents. All of the 24 exons and intron-exon splice sites of OCRL gene were amplified with PCR. Mutations were detected by direct sequencing the PCR products. The infant was found to have carried a c.1499G>A (p.R500Q) mutation in exon 15 of the OCRL gene, which was transmitted from his mother, who was heterozygous for the same mutation. The c.1499G>A mutation, discovered in Chinese population for the first time, has been reported to cause severe Lowe syndrome in other ethnic populations. The c.1499G>A mutation of the OCRL gene is probably responsible for the disease in the patient. Further study of this mutation may facilitate delineation of the genotype-phenotype correlation of this disease.

Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: Recommendation for expanded newborn screening in Hong Kong

ObjectivesTyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. Design and methodsA two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. ResultsThe patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. ConclusionsBecause of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong.

Severe cardiac phenotype of Berardinelli-Seip congenital lipodystrophy in an infant with homozygous E189X BSCL2 mutation

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive condition associating insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Disease-causing mutations have been described in AGPAT2 and BSCL2 genes. Hypertrophic cardiomyopathy is a classical late (third decade) complication which has only been occasionally described in childhood. We report on a 4-month-old Chinese male infant who presented with a severe BSCL “cardiac” phenotype comprising heart failure, hypertension and hypertrophic cardiomyopathy.

Meningitis due to mucoid-encapsulated bacilli. Report of two cases

The bacteriological findings in two fatal cases of meningitis have been described. In the one case, a parturient Chinese female, the causal organism was identified as Bact. aerogenes, in the other, a Chinese male infant aged one month, Bact. friedlönderi. The histopathology of the latter case has been described : the most striking feature was the histiocytic nature of the cellular response.