Case#: patient, M, Age of Report: newborn, Ethnicity: Korean.
CasePresentingHPOs: HP:0004322 (Short stature), HP:0004325 (Decreased body weight), HP:0040195 (Decreased head circumference), HP:0003074 (Hyperglycemia), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0011220 (Prominent forehead), HP:0000490 (Deeply set eye/Ocular depression), HP:0009125 (Lipodystrophy), HP:0000023 (Inguinal hernia), HP:0001642 (Pulmonic stenosis), HP:0001684 (Secundum atrial septal defect/ASD secundum), HP:0000684 (Delayed eruption of teeth)
CaseHPOFreeText: To the best of our knowledge, this is the first case report of SHORT syndrome with TNDM.
The patient was a newborn male and the only child of a healthy non-consanguineous Korean couple with a non-contributory family history. The height of his father and mother was 170 cm (−0.70 SD score) and 160 cm (−0.04 SD score), respectively. They had no dysmorphic features. The mother had regular antenatal check-up and did not have any history of medical and obstetric problems during pregnancy. He was born at 38 weeks of gestation but displayed features of IUGR during pregnancy. His birth weight was 1.8 kg (<3rd percentile), length 44 cm (<3rd percentile), and head circumference 31 cm (<3rd percentile) according to the Korean reference for birth weight based on gestational age and sex. The initial blood glucose level was 70 mg/dl. The baby was exclusively breastfed starting on day 3 and was in generally good condition. However, blood glucose level was between 218 and 263 mg/dl at 5 day of age. At the age of 20 day, his blood glucose level was still high (205–260 mg/dl), and the infant was referred to the endocrine clinic for persistent hyperglycemia assessment. On physical examination, several dysmorphic features (triangular-shaped face, prominent forehead, ocular depression, lipodystrophy at the lumbar region) and inguinal hernia were present. The systolic and diastolic blood pressure measurements were 74 and 42 mmHg, respectively. The serum c-peptide and insulin levels were 2.83 ng/ml (normal: 1.0–3.5) and 120 μU/ml (normal: 2.8–13.5), respectively. Baseline chemistry including serum blood urea nitrogen was 15.3 mg/dl (normal: 7.0–20.0), creatinine 0.9 mg/dl (normal: 0.6–1.2), aspartate aminotransferase 38 U/L (normal: 14–40), and alanine aminotransferase 16 U/L (normal: 9–45), as well as complete blood count profile were within normal range. Urinalysis showed no glucose or ketones. There was no sign of ketoacidosis and the patient had no type 1 diabetes autoantibodies (antibodies against glutamic acid decarboxylase, islet cell, islet antigen-2, and insulin). The liver and pancreas ultrasonography revealed no structural abnormality. Echocardiography at the age of 1 month confirmed mild pulmonary stenosis and ASD secundum (2 mm) which did not require surgical intervention. Neonatal diabetes mellitus (NDM) was suspected on the basis of hyperglycemia occurring within the first month of life that lasted for >2 weeks and required insulin therapy. At age of 25 day, clinical exome sequencing was performed to identify the genetic cause of NDM.
To monitor the glycemic level, his blood glucose was measured at the beginning of each feeding session. The patient was treated with subcutaneous insulin, and blood glucose level gradually stabilized. The blood glucose levels ranged from 110–250 mg/dl during the next 10 days. An adequate glucose level was achieved at 6 weeks of age without insulin treatment. His body weight was 4.4 kg (<3rd percentile) and his length was 61.6 cm (<3rd percentile) at 10 months of age. The patient experienced no hyperglycemic episode and the glycated hemoglobin was 5.0% and insulin level 2.8 μU/ml. At 10 months of age, the patient had no teeth erupted in the oral cavity.
CaseNotHPOs: N/A.
CaseNotHPOFreeText: Urinalysis showed no glucose or ketones. There was no sign of ketoacidosis and the patient had no type 1 diabetes autoantibodies (antibodies against glutamic acid decarboxylase, islet cell, islet antigen-2, and insulin). The liver and pancreas ultrasonography revealed no structural abnormality.
CasePreviousTesting: N/A.
CaseMethod1: N/A.
CaseMethod2: N/A.
CaseGenotypingMethod: TruSight One sequencing panel and Sanger sequencing.
Variant: NM_181523.3:c.1945C>T (p.Arg649Trp).
ClinVar: 60763.
CAID: CA344799.
gnomAD: N/A.
VariantEvidence: N/A.
CaseAddInfo: Segregation analysis could not be performed due to the unavailability of parental samples.
CasePMIDs: N/A.