Objectives: A distinct syndrome characterized by muscle cramps, insulin resistance, acanthosis nigricans and acral hypertrophy (Flier’s syndrome) has been described as a sporadic or an autosomal recessive condition. The patients described so far have no definite weakness or S131 123 specific abnormalities on neurological examination. The muscle cramps occur in proximal muscles and in the calves and worsen after exercise. CK levels in this syndrome are frequently increased, while EMG findings are usually normal. Muscle biopsy can show mild non specific abnormalities. Diphenylhydantoin has been suggested to improve muscle cramps and pain and to a minor degree, to improve glucose intolerance, in a limited number of patients. We describe 3 related and 1 unrelated patient with muscle cramps associated with insulin resistance, acanthosis nigricans, obesity. Methods: The patients were subjected to: (1) physical examination (search for acanthosis nigricans, waist to hip ratio, body mass index- BMI); (2) muscle strength testings; (3) blood tests (CK; plasma hormone levels; fasting insulin, oral glucose tolerance test, homeostasis model assessment-HOMA to quantify the insulin resistance index); (4) EMG; (5) abdomen CT scan; (6) muscle biopsy. Patients were then subjected to: (1) diet and increased physical activity; (2) oral phenytoin 50 mg tid. Results: The diagnostic work-up and differential diagnosis of painful myopathies and high CK is presented in 4 patients, including screening for insulin resistance, led to rule out muscular dystrophies and metabolic myopathies. The findings of mild proximal weakness, high CK, acanthosis nigricans and insulin resistance fulfilled the diagnosis of Flier’s Syndrome. In the most affected patient, phenytoin controlled muscle cramps completely 4 months after starting treatment. Insulin resistance was also reduced significantly (HOMA before treatment: 5.2; HOMA after treatment: 1.68). Conclusions: Unexplained muscle cramps or painful myopathy, in the presence of acanthosis nigricans should alert the clinician towards a possible associated insulin resistant condition. This underlying metabolic disorder should be thoroughly looked for, because despite the degree of severity of the insulin resistance, this may be clinically silent as it was in our patients. The diagnosis of the syndrome of muscle cramps, insulin resistance and acanthosis nigricans has important clinical implications given the treatable nature of this condition.

Muscle cramps, insuline resistance, acanthosis nigricans and acral hypertrphy sindrome : a potentially treatable condition / A. Malavazos, A. Zanolini, V. Sansone, B. Fossati, M.C. Panzeri, G. Meola. ((Intervento presentato al 19. convegno Meeting of the European Neurological Society - ENS tenutosi a Milan nel 2009.

Muscle cramps, insuline resistance, acanthosis nigricans and acral hypertrphy sindrome : a potentially treatable condition

A. Malavazos;V. Sansone;G. Meola
2009

Abstract

Objectives: A distinct syndrome characterized by muscle cramps, insulin resistance, acanthosis nigricans and acral hypertrophy (Flier’s syndrome) has been described as a sporadic or an autosomal recessive condition. The patients described so far have no definite weakness or S131 123 specific abnormalities on neurological examination. The muscle cramps occur in proximal muscles and in the calves and worsen after exercise. CK levels in this syndrome are frequently increased, while EMG findings are usually normal. Muscle biopsy can show mild non specific abnormalities. Diphenylhydantoin has been suggested to improve muscle cramps and pain and to a minor degree, to improve glucose intolerance, in a limited number of patients. We describe 3 related and 1 unrelated patient with muscle cramps associated with insulin resistance, acanthosis nigricans, obesity. Methods: The patients were subjected to: (1) physical examination (search for acanthosis nigricans, waist to hip ratio, body mass index- BMI); (2) muscle strength testings; (3) blood tests (CK; plasma hormone levels; fasting insulin, oral glucose tolerance test, homeostasis model assessment-HOMA to quantify the insulin resistance index); (4) EMG; (5) abdomen CT scan; (6) muscle biopsy. Patients were then subjected to: (1) diet and increased physical activity; (2) oral phenytoin 50 mg tid. Results: The diagnostic work-up and differential diagnosis of painful myopathies and high CK is presented in 4 patients, including screening for insulin resistance, led to rule out muscular dystrophies and metabolic myopathies. The findings of mild proximal weakness, high CK, acanthosis nigricans and insulin resistance fulfilled the diagnosis of Flier’s Syndrome. In the most affected patient, phenytoin controlled muscle cramps completely 4 months after starting treatment. Insulin resistance was also reduced significantly (HOMA before treatment: 5.2; HOMA after treatment: 1.68). Conclusions: Unexplained muscle cramps or painful myopathy, in the presence of acanthosis nigricans should alert the clinician towards a possible associated insulin resistant condition. This underlying metabolic disorder should be thoroughly looked for, because despite the degree of severity of the insulin resistance, this may be clinically silent as it was in our patients. The diagnosis of the syndrome of muscle cramps, insulin resistance and acanthosis nigricans has important clinical implications given the treatable nature of this condition.
22-giu-2009
Muscle cramps ; insuline resistance ; acanthosis nigricans ; acral hypertrophy syndrome
Settore MED/26 - Neurologia
Muscle cramps, insuline resistance, acanthosis nigricans and acral hypertrphy sindrome : a potentially treatable condition / A. Malavazos, A. Zanolini, V. Sansone, B. Fossati, M.C. Panzeri, G. Meola. ((Intervento presentato al 19. convegno Meeting of the European Neurological Society - ENS tenutosi a Milan nel 2009.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/146751
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