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Indian Journal of Medical Sciences, Vol. 59, No. 2, February, 2005, pp. 70-73 Case Report Rabson-mendenhall syndrome Kumar Sarita, Tullu Milind S., Muranjan Mamta N., Kamat Jaishree R. The Genetics Division, Department of Pediatrics, Seth G. S. Medical College and KEM Hospital, Parel, Mumbai - 400 012 Code Number: ms05012 Abstract Rabson-Mendenhall syndrome is characterized by growth retardation, dysmorphisms, lack of subcutaneous fat, acanthosis nigricans, enlarged genitalia, hirsutism, premature and dysplastic dentition, coarse facial features, paradoxical fasting hypoglycemia and post-prandial hyperglycemia, extreme hyperinsulinemia and pineal hyperplasia. We describe a six-month-old female child with physical features suggestive of the Rabson-Mendenhall syndrome. The child also had medullary nephrocalcinosis.KEYWORDS: Diabetes, Hirsutism, Insulin, Ketoacidosis, Nephrocalcinosis, Syndrome INTRODUCTION Severe insulin resistance is caused by genetic defects of the insulin receptor gene (Type A syndrome, Leprechaunism and Rabson-Mendenhall syndrome) or by the presence of circulating auto-antibodies that disrupt the normal functions of the insulin receptor (Type B syndrome).[1] Hyperinsulinemia and severe insulin resistance is associated with impaired glucose tolerance and diabetes mellitus.[1] The Rabson-Mendenhall syndrome (RMS) is characterized by dental and skin abnormalities, hirsutism, acanthosis nigricans and pineal hyperplasia.[1],[2] Herein, we present a case of RMS associated with medullary nephrocalcinosis.CASE REPORT A six-month-old female born of a third-degree consanguineous marriage presented with excessive body hair and abdominal distension noticed since birth. She had history of bilateral purulent ocular discharge since past eight days. Social smile was the only milestone achieved (at 3 months of age). The child had premature eruption of teeth (noted since 3 months of age). Her previous male sibling had abnormal physical features since birth (like the present case) and had expired at the age of 5 months. However, the case records of this sibling were not available with the parents. The patient was born by Caesarean section at term (done in view of fetal distress, intrauterine growth retardation and oligohydramnios) and had birth weight of 1.75 kg.On examination, she had dysmorphisms in the form of coarse senile-appearing facies, large ears, prominent lips, prominent nipples, hirsutism, premature eruption of teeth (total 8 teeth at 6 months of age) and clitoromegaly (3 cm) [Figure - 1] and [Figure - 2]. She had failure to thrive (weight of 2.4 kg) and bilateral corneal abscesses. Systemic examination was normal. Investigations revealed anemia (Hb- 6.3 g%), leukocytosis (17,000/cumm), metabolic acidosis on blood gas examination (pH- 7.22, pO2- 86, pCO2- 28.3, HCO3- 11.9, O2 Sat- 94.8%) with a urine pH of 6.5 and a normal anion gap. The renal parameters were normal. Hypercalciuria and hypocalcemia (6.6 mg%) with low phosphorus levels (2.16 mg%) were detected. Bilateral medullary nephrocalcinosis, presence of Mullerian structures and visualization of right ovary were the features seen on ultrasonography. Random blood sugar level was 32 mg% with a post-feeding blood sugar of 48 mg%. Serum insulin levels were inappropriately high (46.5 units/ml- Normal: 6-27 units/ml). Staphylococcus aureus was isolated from the corneal swab. The child was treated with intravenous fluids, antibiotics and vitamin supplementation. She was discharged after a hospital stay of 10 days. However, the parents did not follow up with the child further. DISCUSSION Rabson and Mendenhall (1956) reported three siblings with dental and skin abnormalities, abdominal distension, phallic enlargement, early dentition, coarse senile-looking facies, striking hirsutism, mental precocity, prognathism, thick fingernails and acanthosis nigricans.[2] Insulin-resistant diabetes mellitus, ketoacidosis, intercurrent infections, pineal hyperplasia and ovarian tumor were also noted by them.[2] Later, West et al (1975) described siblings with similar features.[2] The primary defect in RMS appears to be in the insulin receptors. The gene map locus is 19p13.2.[2] Leprechaunism and RMS are autosomal recessive conditions with abnormal alleles for insulin receptors.[3],[4] Growth retardation, dysmorphisms, lack of subcutaneous fat, acanthosis nigricans, enlarged genitalia, hirsutism, paradoxical fasting hypoglycemia and post-prandial hyperglycemia and extreme hyperinsulinemia is seen in both the conditions.[3] Children with leprechaunism die in infancy, have severe manifestations, do not develop diabetic ketoacidosis and the major problem is fasting hypoglycemia.[3],[5],[6] Cells from most patients with leprechaunism have absent insulin binding.[6] RMS differs from leprechaunism by being less severe, and by the presence of premature and dysplastic dentition, coarse facial features, gingival hyperplasia, pineal hyperplasia, and survival beyond one year of age.[3],[5],[6] The mutations in the insulin receptor gene cause a spectrum of inherited insulin-resistance syndromes ranging from severe leprechaunism to Type A insulin resistance (usually evident after puberty); RMS has an intermediate phenotype with survival beyond one year but death usually before puberty.[4],[5],[6] Our case had features of the Rabson-Mendenhall syndrome.Patients with RMS develop severe and intractable ketoacidosis. There is a paradoxical fasting hypoglycemia and post-prandial hyperglycemia initially in life, followed by constant hyperglycemia (by four years of age) and later constant ketoacidosis by six years of age.[3],[6],[7] Though the insulin levels are extremely elevated initially and then decrease with age, they remain higher than normal values.[3],[6] The paradoxical fasting hypoglycemia is caused by inappropriately elevated insulin levels at the time of fasting, due to excessive production of insulin by the pancreas, coupled with the prolonged half-life of the hormone.[6] Affected patients remain insensitive to exogenous insulin.[4] Ketoacidosis has been shown to reverse by high doses of insulin.[3] The absence of post-prandial hyperglycemia in our case is a surprising finding, which cannot be explained on the basis of our current understanding of the syndrome. Patients with RMS have been treated with high doses of insulin and insulin-sensitizing drugs like metformin and glitazones.[7],[8] Use of recombinant human growth hormone and recombinant human insulin-like growth factor-I have not been associated with encouraging results as far as growth is concerned.[4],[5],[8] Cochran et al have shown a 40-60% decrease in fasting serum glucose and insulin levels and improved glycosylated hemoglobin in two siblings with RMS treated with r-metHuLeptin therapy for 10 months, and a corresponding improvement in glucose and insulin tolerance during the Leptin therapy.[7],[8] There have been attempts to study the genotype-phenotype correlations in inherited severe insulin resistance and it has been noted that mutations markedly impairing insulin binding resulted in the most severe phenotype with early demise, while mutations leaving residual insulin binding activity were associated with longer survival.[6] Leprechaunism and RMS should be considered as a continuous spectrum, in which the specific mutation and the degree of impairment of insulin action predicts the survival, rather than the types of the syndrome.[6] Most of the patients survive till 5-15 years of age.[2],[6],[8] To our knowledge, this is the first case of the Rabson-Mendenhall syndrome associated with medullary nephrocalcinosis. ACKNOWLEDGEMENT The authors thank Dr. N.A. Kshirsagar, Dean- Seth G. S. Medical College & KEM Hospital, Mumbai for granting permission to publish this manuscript. References
Copyright 2005 - Indian Journal of Medical Sciences The following images related to this document are available:Photo images[ms05012f1.jpg] [ms05012f2.jpg] |
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