[Acute heart failure in a neonate]. / æ–°ç”Ÿå„¿æ€¥æ€§å¿ƒåŠŸèƒ½ä¸å ¨1例.

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.

Dihydropyrimidinase enzyme deficiency and congenital isolated adrenocorticotrophin deficiency: dual genetic diagnosis in a Sri Lankan boy.

We report on a male patient who was investigated for frequent apneic episodes, feeding problems, hypotonia, and left-sided middle cerebral artery infarction in the magnetic resonance imaging at 2 weeks of age. Primary diagnosis of dihydropyrimidinase (DPYS) deficiency was suspected following the analysis of urine for organic acid; DPYS deficiency was strongly suggested by the presence of dihydrouracil, thymine, and uracil. Subsequent genetic evaluation by whole exome sequencing revealed 2 separate mutations, homozygous pathogenic variant c.1010T>C p.Leu337Pro of the DPYS gene, resulting in DPYS deficiency, and homozygous pathogenic variant c.535C>T p.Arg179* of TBX19 gene, which is associated with autosomal recessive congenital isolated adrenocorticotrophic hormone deficiency. Currently, the patient is 2 years old, and he has gross motor retardation and seizure disorder. We suggest that the clinical phenotype of the proband can be a result of mixed expression of both mutations.

A Case of Congenital Isolated Adrenocorticotropic Hormone Deficiency Caused by Two Novel Mutations in the TBX19 Gene.

Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (CIAD) is a rare disorder which can result in 20% mortality in the neonatal period if misdiagnosed. A 2 years and 7 months old boy was hospitalized many times because of recurrent hypoglycemia. On initial physical examination, the patient showed special appearance and indications of fast growth (≥P97). Laboratory investigations revealed low levels of ACTH and cortisol in his plasma. Except thyroid-stimulating hormone, the anterior pituitary hormone concentrations were normal. Molecular data showed compound heterozygosity for two novel mutations in the TBX19 gene (encoding the transcription factor T-Box 19). Mutation c.205C>T was inherited from mother and the fragment deletion (from g.168,247,374 to g.168,278,264) was from father. Hydrocortisone replacement therapy was effective. We reported two novel TBX19 mutations, expanding the mutation spectrum of this disorder, in a CIAD patient who presented with special appearance, signs of fast growth, and thyroid-stimulating hormone derangement. In addition, for avoiding misdiagnosis, criterion for ACTH and cortisol detection of CIAD should be established.

A rare cause of neonatal hypoglycemia in two siblings: TBX19 gene mutation.

Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rarely seen disease characterized by low serum ACTH and cortisol levels accompanied by normal levels of the other anterior pituitary hormones. In these patients, severe hypoglycemia, convulsions, and prolonged cholestatic jaundice are expected findings in the neonatal period. In this paper, we present two siblings with TBX19 gene mutation. The first case was investigated at the age of 2 months for severe hypoglycemia, recurrent convulsions, and prolonged cholestatic jaundice persisting since the neonatal period. The second sibling presented with hypoglycemia in the neonatal period. In both cases, baseline cortisol and ACTH levels were low and cortisol response to the low-dose ACTH test was inadequate, while all other anterior pituitary hormones were normal. Thus, IAD was suspected. Genetic analysis of the TBX19 gene was performed. Both cases were homozygous for c.856 C>T (p.R286*), and hydrocortisone treatment was initiated. The first patient did not attend the clinic regularly. On attendance at another hospital, hydrocortisone treatment was discontinued and antiepileptic treatment was initiated because of suspected epilepsy. This led to developmental delay, measured with the Denver Developmental Screening Test II (DDST-II), because of cessation of the hydrocortisone therapy. The second sibling had normal development, as measured with the DDST. In conclusion, TBX19 gene analysis must be performed if adrenal insufficiency is associated with isolated ACTH deficiency. Delay in diagnosis may lead to inappropriate diagnoses, such as epilepsy, and thus inappropriate therapy, which may result in neonatal mortality.

A Novel TBX19 Gene Mutation in a Case of Congenital Isolated Adrenocorticotropic Hormone Deficiency Presenting with Recurrent Respiratory Tract Infections.

INTRODUCTION: Congenital isolated adrenocorticotropic hormone deficiency (CIAD) is a rare disease characterized by low adrenocorticotropic hormone (ACTH) and cortisol levels. To date, recurrent pulmonary infections in infancy have not been reported as an accompanying symptom of CIAD. CASE PRESENTATION: A 7-year-old boy was hospitalized nine times for recurrent lower respiratory tract infections. The results of all tests for the possible causes of wheezing were within the normal limits. His ACTH and cortisol levels were persistently low. All other pituitary hormone levels, and adrenal ultrasound and pituitary magnetic resonance imaging results, were normal. Molecular analyses confirmed the diagnosis of CIAD by identifying compound heterozygosity for two mutations in the TBX19 gene. The first was a novel frameshift c.665delG variant in exon 4 of the TBX19 gene, leading to premature termination that was predicted to result in a non-functional truncated protein. The second was a nonsense C-to-T transition in exon 6 of the TBX19 gene, resulting in an arg286-to-ter mutation (dbSNP: rs74315376). Both parents were heterozygous for one of the mutations. CONCLUSION: Here, we presented a new mutation in the TBX19 gene in a patient with CIAD who presented with recurrent respiratory tract infections. This expands the mutation spectrum in this disorder. To conclude, adrenal insufficiency should be considered in patients with unexplained recurrent infections to prevent a delay in diagnosis.