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Diabetes mellitus may be the earliest and sole manifestation of the H syndrome

2009; Wiley; Volume: 26; Issue: 11 Linguagem: Inglês

10.1111/j.1464-5491.2009.02843.x

1464-5491

Valentina Broshtilova, Yuval Ramot, Vered Molho‐Pessach, Abraham Zlotogorski,

Pancreatic function and diabetes

The H syndrome is a recently reported autosomal recessive disease with variable inter- and intra-familial clinical manifestations. The clinical, histopathological and molecular findings have been described in detail [1–3]. The major clinical findings include cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, hallux valgus and hyperglycaemia/diabetes mellitus. Less common manifestations include facial telangiectasia, proptosis, ocular arcus senilis and dilated scleral vascularization, gynaecomastia, scrotal masses, varicose veins, malabsorption, lipoatrophy of the lateral buttocks and fixed flexion contractures of the toe joints and the proximal interphalangeal joints. The principle histological finding is inflammatory infiltrate consisting mainly of histiocytes, which is later replaced by deep dermal and subcutaneous fibrosis. Anaemia, mild to severe, and elevated erythrocyte sedimentation rate (usually more than 100 mm/h) are among the most common laboratory findings. The syndrome is caused by mutations in the human equilibrative nucleoside transporter 3 (hENT3) [1]. Despite the vast range of clinical phenotypes described above, some patients may have only one symptom at presentation, such as gynaecomastia or dilated scleral vascularization [1]. It is important to note that the disease has a progressive nature (e.g. patient may present with mild camptodactyly, later progressing to severe flexion contractures of the hands and feet) and symptoms accumulate with age. We reported previously that a Bulgarian patient [1], carrying the homozygous p.G427S mutation, showed a full range of H syndrome symptoms from the age of 10 years, including cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, gynaecomastia, hypogonadism, facial telangiectases, proptosis, bilateral camptodactyly, malabsorption and diabetes mellitus, first appearing as ketoacidosis at age 14 years. His older brother was not available at the time of the initial examination and was reported to have only diabetes mellitus which presented at age 22 years, with ketoacidosis (glucose 24.8 mmol/l) and with negative anti-glutamic acid decarboxylase (GAD) antibody, without any other manifestations suggestive of the H syndrome. Recently, we found that the older brother also carries the same p.G427S homozygous mutation. Further examination of this patient at age 26 years revealed that he had developed some telangiectases at age 24 years. No other major or minor clinical findings were identified, except for mild non-specific short stature (1.60 m). No diabetic complications were observed. The patient’s weight was 56 kg, with a body mass index (BMI) of 21.9 kg/m2. His prescribed medication consisted of 30 units of Actrapid® and 18 units of Mixtard 30/70® (Novo Nordisk, Bagsværd, Denmark) daily. Glycated haemoglobin (HbA1c) was 7.2% and total cholesterol 3.2 mmol/l, high-density lipoprotein (HDL) 1.64 mmol/l and low-density lipoprotein (LDL) 2.8 mmol/l. Other laboratory findings were in the normal ranges [e.g. erythrocyte sedimentation rate (ESR) 13 mm/h, haemoglobin 14 g/dl]. In recent years it has become clear that not all diabetes cases presenting in childhood and adolescence are of Type 1 and c. 5% of cases are diagnosed as non-Type 1 diabetes [4]. Of these patients, about 10% have syndromic diabetes, which may be caused by a limited number of conditions. It is essential to recognize these syndromes early in order to identify treatable complications and potential treatment modalities, and for performing genetic testing of other family members [4]. Diabetes is a variable finding in the H syndrome, seen in approximately 20% of cases. Nevertheless, the patient presented herein shows the significance of including the H syndrome in the differential diagnoses of early onset diabetes mellitus. We conclude that diabetes mellitus may be the presenting and sole symptom of this disease. Nothing to declare. Both brothers provided written informed consent for publication of this article. The work presented in this letter was supported in part by the Authority for Research and Development, Hebrew University of Jerusalem (to AZ).