Unusual manifestations of young woman with MODY5 based on 17q12 recurrent deletion syndrome

Abstract

Background Maturity-onset diabetes of the young type 5 (MODY5) is a rare subtype of MODYs. It is caused by mutations of the hepatocyte nuclear factor 1 homeobox b gene (HNF1B). 17q12 recurrent deletion syndrome usually results in MODY5 because of the deletion of HNF1B. These patients often have other clinical manifestations besides diabetes. Refractory hypomagnesemia was a clue for further examination in this patient. But she lacked structural abnormalities of the genitourinary system and neurodevelopmental disorders that are common manifestations in patients with 17q12 recurrent deletion syndrome. Some atypical patients deserved attention. Case presentation A 21-year-old young woman was admitted to our hospital for severe malnutrition and gastrointestinal symptoms. At age 20, she was diagnosed with type 2 diabetes mellitus (T2DM) and was administered oral antidiabetic drugs. Soon afterward, the patient discontinued the medication on her own accord and then went to the hospital again due to diabetic ketoacidosis. After insulin treatment, diabetic ketoacidosis was cured and blood glucose was controlled satisfactorily. But intractable nausea, vomiting, and persistent weight loss were stubborn. Further examination revealed that the patient had hypokalemia and hard rectification hypomagnesemia. Genetic testing revealed about 1.85 Mb heterozygous fragment deletion on chromosome 17 and deletion of exons 1–9 of HNF1B heterozygosity missing was approved. Finally, the patient was diagnosed MODY5. Discussion and Conclusions The 17q12 recurrent deletion syndrome is characterized by MODY5, structural or functional abnormalities of the kidney and urinary tract, and neurodevelopmental or neuropsychiatric disorders. This patient did not have any structural abnormalities of the genitourinary system and neuropsychiatric disorders, which is rare. She had experienced a period of misdiagnosis before being diagnosed with 17q12 recurrent deletion syndrome, and hypomagnesemia was an important clue for her diagnosis. Therefore, diabetic physicians should be alert to a special type of diabetes if patients have unexplained signs and symptoms. The absence of well-known features of HNF1B disease does not exclude MODY5.

17q12 Microdeletion Syndrome as a Rare Cause of Elevated Liver Enzymes: Case Report and Literature Review

“…Elevated liver enzymes were also noticed in our patient during her annual nephrology follow-up with a chief complaint of pruritis. However, gastrointestinal manifestations were less common features associated with 17q12 deletion syndrome [5] and the reported cases with elevated liver enzymes were asymptomatic [8,9,12,13].…”

“…Despite being an autosomal dominant syndrome, upon reviewing the previously reported cases during the past 13 years, a slightly higher prevalence of 17q12 recurrent deletion syndrome among females was noted [3,5,8,6,[11][12][13][14][15] (Table 1). Our patient was an 11-year-old female which is in line with the previously reported cases in terms of sex.…”

“…However, most of the cases were diagnosed in late adulthood. Late diagnosis might be due to the absence of the well-known features of the 17q12 syndrome or misdiagnosing MODY5 [5].…”

“…Magnesium impairment may occur in patients with 17q12 deletion syndrome and can be an atypical leading clue in the diagnosis of this syndrome. Chen et al [5] and Perovsic et al [4], determined that refractory hypomagnesemia is an important atypical predictor for 17q12 syndrome. Cheng et al [5] reported a case of a 21-year-old female who was misdiagnosed initially with type 2 diabetes mellitus at age of 20 and refractory hypomagnesemia was the earliest clue for her diagnosis with MODY5 in the absence of well-known features of 17q12 syndrome [5], whereas Perosvic et al [4] identified a case of a male patient who presented with ureteropelvic junction obstruction, chronic hydronephrosis, mild cognitive impairment, marfanoid features, and refractory hypomagnesemia.…”

“…HNF1B gene belongs to the homeodomain-containing family of transcription factors whose mutation contributes to renal, hepatic, pancreatic, and urogenital tract disorders as it is involved in the organogenesis of the previously mentioned organs [2,5,6]. HNF1B gene mutation is a cause of MODY5 and renal abnormalities [2,5,7,8] that should be considered during screening for the disease or after the diagnosis is made, especially if there is renal involvement [7,9]. The LHX1 gene is responsible for early brain development and cognitive functions [8].…”